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Coronavirus: Global Response Urgently Needed

15 March 2020

Jim O'Neill

Chair, Chatham House

Robin Niblett

Director and Chief Executive, Chatham House

Creon Butler

Research Director, Trade, Investment & New Governance Models: Director, Global Economy and Finance Programme
There have been warnings for several years that world leaders would find it hard to manage a new global crisis in today’s more confrontational, protectionist and nativist political environment.

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A currency dealer wearing a face mask monitors exchange rates in front of a screen showing South Korea's benchmark stock index in Seoul on March 13, 2020. Photo by JUNG YEON-JE/AFP via Getty Images.

An infectious disease outbreak has long been a top national security risk in several countries, but the speed and extent of COVID-19’s spread and the scale of its social and economic impact has come as an enormous and deeply worrying shock.

This pandemic is not just a global medical and economic emergency. It could also prove a decisive make-or-break point for today’s system of global political and economic cooperation.

This system was built up painstakingly after 1945 as a response to the beggar-thy-neighbour economic policies of the 1930s which led to the Second World War. But it has been seriously weakened recently as the US and China have entered a more overt phase of strategic competition, and as they and a number of the other most important global and regional players have pursued their narrowly defined self-interest.

Now, the disjointed global economic response to COVID-19, with its enormous ramifications for global prosperity and economic stability, has blown into the open the urgent need for an immediate reaffirmation of international political and economic cooperation.

What is needed is a clear, coordinated and public statement from the leaders of the world’s major countries affirming the many things on which they do already agree, and some on which they should be able to agree.

In particular that:

  • they will give the strongest possible support for the WHO in leading the medical response internationally;
  • they will be transparent and tell the truth to their peoples about the progress of the disease and the threat that it represents;
  • they will work together and with the international financial institutions to provide businesses, particularly SMEs, and individuals whatever support they need to get through the immediate crisis and avoid long-term damage to the global economy; 
  • they will ensure the financial facilities for crisis support to countries - whether at global or regional level - have whatever resources they need to support countries in difficulty;
  • they will avoid new protectionist policies - whether in trade or finance;
  • they commit not to forget the poor and vulnerable in society and those least able to look after themselves.

Such a statement could be made by G20 leaders, reflecting the group’s role since 2010 as the premier forum for international economic cooperation.

But it could be even more appropriate coming from the UN Security Council, recognising that COVID-19 is much more than an economic challenge; and also reflecting the practical fact, in a time when international travel is restricted, the UNSC has an existing mechanism in New York to negotiate and quickly agree such a statement.

A public statement by leading countries could do a great deal to help arrest a growing sense of powerlessness among citizens and loss of confidence among businesses worldwide as the virus spreads.

It could also set a new course for international political and economic cooperation, not just in relation to the virus, but also other global threats with potentially devastating consequences for economic growth and political stability in the coming years.




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America's Coronavirus Response Is Shaped By Its Federal Structure

16 March 2020

Dr Leslie Vinjamuri

Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme
The apparent capacity of centralized state authority to respond effectively and rapidly is making headlines. In the United States, the opposite has been true.

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Harvard asked its students to move out of their dorms due to the coronavirus risk, with all classes moving online. Photo by Maddie Meyer/Getty Images.

As coronavirus spreads across the globe, states grapple to find the ideal strategy for coping with the global pandemic. And, in China, Singapore, South Korea, the US, the UK, and Europe, divergent policies are a product of state capacity and legal authority, but they also reveal competing views about the optimal role of centralized state authority, federalism, and the private sector.

Although it is too soon to know the longer-term effects, the apparent capacity of centralized state authority in China, South Korea and Singapore to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. 

America’s response is being shaped by its federal structure, a dynamic private sector, and a culture of civic engagement. In the three weeks since the first US case of coronavirus was confirmed, state leaders, public health institutions, corporations, universities and churches have been at the vanguard of the nation’s effort to mitigate its spread.

Images of safety workers in hazmat suits disinfecting offices of multinational corporations and university campuses populate American Facebook pages. The contrast to the White House effort to manage the message, downplay, then rapidly escalate its estimation of the crisis is stark.

Bewildering response

For European onlookers, the absence of a clear and focused response from the White House is bewildering. By the time President Donald Trump declared a national emergency, several state emergencies had already been called, universities had shifted to online learning, and churches had begun to close.

By contrast, in Italy, France, Spain and Germany, the state has led national efforts to shutter borders and schools. In the UK, schools are largely remaining open as Prime Minister Boris Johnson has declared a strategy defined by herd immunity, which hinges on exposing resilient populations to the virus.

But America has never shared Europe’s conviction that the state must lead. The Center for Disease Control and Prevention, the leading national public health institute and a US federal agency, has attempted to set a benchmark for assessing the crisis and advising the nation. But in this instance, its response has been slowed due to faults in the initial tests it attempted to rollout. The Federal Reserve has moved early to cut interest rates and cut them again even further this week.

But states were the real first movers in America’s response and have been using their authority to declare a state of emergency independent of the declaration of a national emergency. This has allowed states to mobilize critical resources, and to pressure cities into action. After several days delay and intense public pressure, New York Governor Andrew Cuomo forced New York City Mayor Bill de Blasio to close the city’s schools.

Declarations of state emergencies by individual states have given corporations, universities and churches the freedom and legitimacy to move rapidly, and ahead of the federal government, to halt the spread in their communities.

Washington state was the first to declare a state of emergency. Amazon, one of the state’s leading employers, quickly announced a halt to all international travel and, alongside Microsoft, donated $1million to a rapid-response Seattle-based emergency funds. States have nudged their corporations to be first movers in the sector’s coronavirus response. But corporations have willingly taken up the challenge, often getting ahead of state as well as federal action.

Google moved rapidly to announce a move allowing employees to work from home after California declared a state of emergency. Facebook soon followed with an even more stringent policy, insisting employees work from home. Both companies have also met with World Health Organization (WHO) officials to talk about responses, and provided early funding for WHO’s Solidarity Response Fund set up in partnership with the UN Foundation and the Swiss Philanthropy Foundation.

America’s leading research universities, uniquely positioned with in-house public health and legal expertise, have also been driving preventive efforts. Just days after Washington declared a state of emergency, the University of Washington became the first to announce an end to classroom teaching and move courses online. A similar pattern followed at Stanford, Harvard, Princeton and Columbia - each also following the declaration of a state of emergency.

In addition, the decision by the Church of the Latter Day Saints to cancel its services worldwide followed Utah’s declaration of a state of emergency.

The gaping hole in the US response has been the national government. President Trump’s declaration of a national emergency came late, and his decision to ban travel from Europe but - at least initially - exclude the UK, created uncertainty and concern that the White House response is as much driven by politics as evidence.

This may soon change, as the House of Representatives has passed a COVID-19 response bill that the Senate will consider. These moves are vital to supporting state and private efforts to mobilize an effective response to a national and global crisis.

Need for public oversight

In the absence of greater coordination and leadership from the centre, the US response will pale in comparison to China’s dramatic moves to halt the spread. The chaos across America’s airports shows the need for public oversight. As New York State Governor Cuomo pleaded for federal government support to build new hospitals, he said: ‘I can’t do it. You can’t leave it to the states.'

When it comes to global pandemics, we may be discovering that authoritarian states can have a short-term advantage, but already Iran’s response demonstrates that this is not universally the case. Over time, the record across authoritarian states as they tackle the coronavirus will become more apparent, and it is likely to be mixed.

Open societies remain essential. Prevention requires innovation, creativity, open sharing of information, and the ability to inspire and mobilize international cooperation. The state is certainly necessary, but it is not sufficient alone.




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Coronavirus: All Citizens Need an Income Support

16 March 2020

Jim O'Neill

Chair, Chatham House
We cannot expect policies such as the dramatic monetary steps announced by the Federal Reserve Board and others like it, to end this crisis. A People's Quantitative Easing (QE) could be the answer.

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Delivery bike rider wearing a face mask as a precaution against coronavirus at Madrid Rio park. Photo by Pablo Cuadra/Getty Images.

Linked to the call for a global response to the Covid-19 pandemic that I, Robin Niblett and Creon Butler have outlined, the case for a specific dramatic economic policy gesture from many policymakers in large economies is prescient.

It may not be warranted from all G20 nations, although given the uncertainties, and the desire to show collective initiative, I think it should be G20 driven and inclusive.

We need some sort of income support for all our citizens, whether employees or employers. Perhaps one might call it a truly People’s QE (quantitative easing).

Against the background of the previous economic crisis from 2008, and the apparent difficulties that more traditional forms of economic stimulus have faced in trying to help their economies and their people - especially against a background of low wage growth, and both actual, and perception of rising inequality - other ideas have emerged.

Central banks printing money

Both modern monetary theory (MMT) and universal basic income (UBI) essentially owe their roots to the judgement that conventional economic policies have not been helping.

At the core of these views is the notion of giving money to people, especially lower income people, directly paid for by our central banks printing money. Until recently, I found myself having very little sympathy with these views but, as a result of COVID-19, I have changed my mind.

This crisis is extraordinary in so far as it is both a colossal demand shock and an even bigger colossal supply shock. The crisis epicentre has shifted from China - and perhaps the rest of Asia - to Europe and the United States. We cannot expect policies, however unconventional by modern times, such as the dramatic monetary steps announced by the Federal Reserve Board and others like it, to put a floor under this crisis.

We are consciously asking our people to stop going out, stop travelling, not go to their offices - in essence, curtailing all forms of normal economic life. The only ones not impacted are those who entirely work through cyberspace. But even they have to buy some forms of consumer goods such as food and, even if they order online, someone has to deliver it.

As a result, markets are, correctly, worrying about a collapse of economic activity and, with it, a collapse of companies, not just their earnings. Expansion of central bank balance sheets is not going to do anything to help that, unless it is just banks we are again worried about saving.

What is needed in current circumstances, are steps to make each of us believe with high confidence that, if we take the advice from our medical experts, especially if we self-isolate and deliberately restrict our personal incomes, then we will have this made good by our governments. In essence, we need smart, persuasive People’s QE.

Having discussed the idea with a couple of economic experts, there are considerable difficulties with moving beyond the simple concept. In the US for example, I believe the Federal Reserve is legally constrained from pursuing a direct transfer of cash to individuals or companies, and this may be true elsewhere.

But this is easily surmounted by fiscal authorities issuing a special bond, the proceeds of which could be transferred to individuals and business owners. And central banks could easily finance such bonds.

It is also the case that such a step would encroach on the perception and actuality of central bank independence, but I would be among those that argue central banks can only operate this independence if done wisely. Others will argue that, in the spirit of the equality debate, any income support should be targeted towards those on very low incomes, while higher earners or large businesses, shouldn’t be given any, or very little.

I can sympathise with such spirit, but this also ignores the centrality of this particular economic shock. All of our cafes and restaurants, and many of our airlines, and such are at genuine risk of not being able to survive, and these organisations are considerable employers of people on income.

It is also the case that time is of the essence, and we need our policymakers to act as soon as possible, otherwise the transmission mechanisms, including those about the permanent operation of our post World War 2 form of life may be challenged.

We need some kind of smart People’s QE now.




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COVID-19 Impact on Refugees is Also Political

31 March 2020

Dr Lina Khatib

Director, Middle East and North Africa Programme
The spread of coronavirus in the Levant puts Syrian as well as other refugees and internally displaced people at particular risk because of the policies and practices of the authorities.

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The word Corona written in the sand on the beach in Lebanon's southern city of Saida. amid the spread of coronavirus in the country. Photo by MAHMOUD ZAYYAT/AFP via Getty Images.

As Lebanon strains to contain COVID-19, it is not clear which governmental public health policies apply to refugees. The government announced free testing for coronavirus in the public Rafiq Hariri University Hospital in Beirut but has not mentioned if refugees are eligible.

Lebanon’s coronavirus containment strategy is based on self-reporting and, given incidents of forced deportation and harassment of Syrian refugees from both the authorities and local communities, it is certainly less likely refugees would present themselves to the health authorities for fear of deportation.

Despite agreeing a Lebanon Crisis Response Plan with the UN for refugees, different ministries were left to implement it without coordination, just as Lebanese politicians from all sides started trying to rally popular support for ridding Lebanon from refugees - in particular from Syria, who Lebanese leaders say are causing a strain on the country’s already weak infrastructure.

This finger pointing is coupled with the leaders’ own complete disregard for the rampant corruption and lack of accountability within Lebanon’s political class, which contribute to the weakening of the country’s infrastructure.

For refugees who do find themselves back in Syria, there are different challenges according to which area they are in. In the north-east, the WHO and international NGOs (INGOs) negotiate with both Kurdish authorities as well as the government - each presenting its own hurdles.

Kurdish authorities in northeast Syria have closed the Semalka border with Iraqi Kurdistan, posing a serious dilemma for INGOs offering services in north-east Syria but concerned about their staff safety whose movement is now curtailed.

The government of Syria has stipulated all emergency response must go through its ministries. But this limits what the WHO can do in the country and gives Syrian authorities the ability to block ‘cross-line aid’ which goes from government-controlled to non-government areas.

Despite reports that doctors raised the alarm about suspected cases well before patient zero was confirmed, the government appears to be either covering up the actual extent of the spread of COVID-19 or failing to respond. Some limited testing kits have arrived but testing has barely started.

The WHO’s Syria plan is divided into three regions (north-west, north-east, and areas under government control). But concerns remain as to how workable such a decentralized plan is because of the government’s practices. In January, the UN Security Council did not renew the cross-border response resolution for the Yaroubiye border crossing between Syria and Iraq that the WHO was using to send medical supplies into north-east Syria.

Syrian authorities do not permit recently authorized ‘cross-line’ responders to engage with non-government authorities in areas outside regime control. This essentially voids the authorization to work cross-line as it is practically impossible to implement programs. The WHO has sought approval from the Syrian Ministry of Foreign Affairs to move medical supplies by land to north-east Syria.

While promising facilitation, the Ministry’s reply comes with conditions of seeking detailed approval for every shipment. When Eastern Ghouta was under siege, similar conditions led to certain supplies being removed from UN/ICRC convoys to Eastern Ghouta, and there is no guarantee this will not happen again.

Due to lack of capacity in north-east Syria, coronavirus tests conducted by the WHO there must be processed through the Central Public Health Laboratory in Damascus. Samples are transported twice a week from Qamishli to Damascus but no results were ever received from Damascus for those tests.

While the WHO is able to coordinate access to north-west Syria with the Turkish authorities, the prospective coronavirus testing capacity in the Idlib region is low – despite claims that thousands of kits are arriving, a lack of resource on the ground means potentially only 20 tests per day could be done in an area inhabited by an estimated three million people.

Following the recently announced ceasefire in the area, many internally displaced people are returning from the Turkish border to their homes in the north-west, but such mass movement increases the risk of coronavirus spreading. People also continue to move between Syria, Iraq, Turkey and Lebanon, posing a challenge to the WHO’s COVID-19 response in the Levant, as the WHO has distinct response plans for each country in the region and it is difficult to coordinate across these plans.

Challenges face refugees even if they head towards Europe due to the potential for conflation between migration control and coronavirus outbreak control. Aurelie Ponthieu, Coordinator for Forced Migration at Médecins Sans Frontières (MSF) says there is a risk some countries could use COVID-19 to impose draconian measures towards asylum seekers.

The crisis has also put a halt to search and rescue operations in the Mediterranean because European countries are not allowing boats carrying migrants to disembark under the pretext of limiting the spread of coronavirus. And for migrants who already made it - such as in Greece - they are now being put in collective quarantines in asylum centers, often with poor medical facilities.

Ponthieu also reports that migrants being quarantined on overcrowded navy ships docked in Greek ports, making social distancing impossible. And she is concerned the Greek authorities are imposing a curfew on asylum seekers but not on the local population.

UNHCR is stressing that people’s right of asylum must not be overruled by concerns about the spread of coronavirus, while local and international NGOs across the Levant are trying to coordinate their advocacy on lifting restrictions on freedom of movement for humanitarian workers and on other policies and practices by authorities in the region which are adversely affecting refugee and other vulnerable communities.

The international community must not lose sight of the impact of the crisis on refugees and migrants. It is not enough simply to supply humanitarian and medical assistance without paying attention to the policies and practices of the different authorities who have direct control over the fate of vulnerable communities.

The author would like to thank Aurelie Ponthieu and the two INGO field workers who all agreed to be interviewed to inform this analysis piece.




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Predictions and Policymaking: Complex Modelling Beyond COVID-19

1 April 2020

Yasmin Afina

Research Assistant, International Security Programme

Calum Inverarity

Research Analyst and Coordinator, International Security Programme
The COVID-19 pandemic has highlighted the potential of complex systems modelling for policymaking but it is crucial to also understand its limitations.

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A member of the media wearing a protective face mask works in Downing Street where Britain's Prime Minister Boris Johnson is self-isolating in central London, 27 March 2020. Photo by TOLGA AKMEN/AFP via Getty Images.

Complex systems models have played a significant role in informing and shaping the public health measures adopted by governments in the context of the COVID-19 pandemic. For instance, modelling carried out by a team at Imperial College London is widely reported to have driven the approach in the UK from a strategy of mitigation to one of suppression.

Complex systems modelling will increasingly feed into policymaking by predicting a range of potential correlations, results and outcomes based on a set of parameters, assumptions, data and pre-defined interactions. It is already instrumental in developing risk mitigation and resilience measures to address and prepare for existential crises such as pandemics, prospects of a nuclear war, as well as climate change.

The human factor

In the end, model-driven approaches must stand up to the test of real-life data. Modelling for policymaking must take into account a number of caveats and limitations. Models are developed to help answer specific questions, and their predictions will depend on the hypotheses and definitions set by the modellers, which are subject to their individual and collective biases and assumptions. For instance, the models developed by Imperial College came with the caveated assumption that a policy of social distancing for people over 70 will have a 75 per cent compliance rate. This assumption is based on the modellers’ own perceptions of demographics and society, and may not reflect all societal factors that could impact this compliance rate in real life, such as gender, age, ethnicity, genetic diversity, economic stability, as well as access to food, supplies and healthcare. This is why modelling benefits from a cognitively diverse team who bring a wide range of knowledge and understanding to the early creation of a model.

The potential of artificial intelligence

Machine learning, or artificial intelligence (AI), has the potential to advance the capacity and accuracy of modelling techniques by identifying new patterns and interactions, and overcoming some of the limitations resulting from human assumptions and bias. Yet, increasing reliance on these techniques raises the issue of explainability. Policymakers need to be fully aware and understand the model, assumptions and input data behind any predictions and must be able to communicate this aspect of modelling in order to uphold democratic accountability and transparency in public decision-making.

In addition, models using machine learning techniques require extensive amounts of data, which must also be of high quality and as free from bias as possible to ensure accuracy and address the issues at stake. Although technology may be used in the process (i.e. automated extraction and processing of information with big data), data is ultimately created, collected, aggregated and analysed by and for human users. Datasets will reflect the individual and collective biases and assumptions of those creating, collecting, processing and analysing this data. Algorithmic bias is inevitable, and it is essential that policy- and decision-makers are fully aware of how reliable the systems are, as well as their potential social implications.

The age of distrust

Increasing use of emerging technologies for data- and evidence-based policymaking is taking place, paradoxically, in an era of growing mistrust towards expertise and experts, as infamously surmised by Michael Gove. Policymakers and subject-matter experts have faced increased public scrutiny of their findings and the resultant policies that they have been used to justify.

This distrust and scepticism within public discourse has only been fuelled by an ever-increasing availability of diffuse sources of information, not all of which are verifiable and robust. This has caused tension between experts, policymakers and public, which has led to conflicts and uncertainty over what data and predictions can be trusted, and to what degree. This dynamic is exacerbated when considering that certain individuals may purposefully misappropriate, or simply misinterpret, data to support their argument or policies. Politicians are presently considered the least trusted professionals by the UK public, highlighting the importance of better and more effective communication between the scientific community, policymakers and the populations affected by policy decisions.

Acknowledging limitations

While measures can and should be built in to improve the transparency and robustness of scientific models in order to counteract these common criticisms, it is important to acknowledge that there are limitations to the steps that can be taken. This is particularly the case when dealing with predictions of future events, which inherently involve degrees of uncertainty that cannot be fully accounted for by human or machine. As a result, if not carefully considered and communicated, the increased use of complex modelling in policymaking holds the potential to undermine and obfuscate the policymaking process, which may contribute towards significant mistakes being made, increased uncertainty, lack of trust in the models and in the political process and further disaffection of citizens.

The potential contribution of complexity modelling to the work of policymakers is undeniable. However, it is imperative to appreciate the inner workings and limitations of these models, such as the biases that underpin their functioning and the uncertainties that they will not be fully capable of accounting for, in spite of their immense power. They must be tested against the data, again and again, as new information becomes available or there is a risk of scientific models becoming embroiled in partisan politicization and potentially weaponized for political purposes. It is therefore important not to consider these models as oracles, but instead as one of many contributions to the process of policymaking.




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Supporting NHS Cybersecurity During COVID-19 is Vital

2 April 2020

Joyce Hakmeh

Senior Research Fellow, International Security Programme; Co-Editor, Journal of Cyber Policy
The current crisis is an opportunity for the UK government to show agility in how it deals with cyber threats and how it cooperates with the private sector in creating cyber resilience.

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Nurse uses a wireless electronic tablet to order medicines from the pharmacy at The Queen Elizabeth Hospital, Birmingham, England. Photo by Christopher Furlong/Getty Images.

The World Health Organization, US Department of Health and Human Services, and hospitals in Spain, France and the Czech Republic have all suffered cyberattacks during the ongoing COVID-19 crisis.

In the Czech Republic, a successful attack targeted a hospital with one of the country’s biggest COVID-19 testing laboratories, forcing its entire IT network to shut down, urgent surgical operations to be rescheduled, and patients to be moved to nearby hospitals. The attack also delayed dozens of COVID-19 test results and affected the hospital’s data transfer and storage, affecting the healthcare the hospital could provide.

In the UK, the National Health Service (NHS) is already in crisis mode, focused on providing beds and ventilators to respond to one of the largest peacetime threats ever faced. But supporting the health sector goes beyond increasing human resources and equipment capacity.

Health services ill-prepared

Cybersecurity support, both at organizational and individual level, is critical so health professionals can carry on saving lives, safely and securely. Yet this support is currently missing and the health services may be ill-prepared to deal with the aftermath of potential cyberattacks.

When the NHS was hit by the Wannacry ransomware attack in 2017 - one of the largest cyberattacks the UK has witnessed to date – it caused massive disruption, with at least 80 of the 236 trusts across England affected and thousands of appointments and operations cancelled. Fortunately, a ‘kill-switch’ activated by a cybersecurity researcher quickly brought it to a halt.

But the UK’s National Cyber Security Centre (NCSC), has been warning for some time against a cyber attack targeting national critical infrastructure sectors, including the health sector. A similar attack, known as category one (C1) attack, could cripple the UK with devastating consequences. It could happen and we should be prepared.

Although the NHS has taken measures since Wannacry to improve cybersecurity, its enormous IT networks, legacy equipment and the overlap between the operational and information technology (OT/IT) does mean mitigating current potential threats are beyond its ability.

And the threats have radically increased. More NHS staff with access to critical systems and patient health records are increasingly working remotely. The NHS has also extended its physical presence with new premises, such as the Nightingale hospital, potentially the largest temporary hospital in the world.

Radical change frequently means proper cybersecurity protocols are not put in place. Even existing cybersecurity processes had to be side-stepped because of the outbreak, such as the decision by NHS Digital to delay its annual cybersecurity audit until September. During this audit, health and care organizations submit data security and protection toolkits to regulators setting out their cybersecurity and cyber resilience levels.

The decision to delay was made to allow the NHS organizations to focus capacity on responding to COVID-19, but cybersecurity was highlighted as a high risk, and the importance of NHS and Social Care remaining resilient to cyberattacks was stressed.

The NHS is stretched to breaking point. Expecting it to be on top of its cybersecurity during these exceptionally challenging times is unrealistic, and could actually add to the existing risk.

Now is the time where new partnerships and support models should be emerging to support the NHS and help build its resilience. Now is the time where innovative public-private partnerships on cybersecurity should be formed.

Similar to the economic package from the UK chancellor and innovative thinking on ventilator production, the government should oversee a scheme calling on the large cybersecurity capacity within the private sector to step in and assist the NHS. This support can be delivered in many different ways, but it must be mobilized swiftly.

The NCSC for instance has led the formation of the Cyber Security Information Sharing Partnership (CiSP)— a joint industry and UK government initiative to exchange cyber threat information confidentially in real time with the aim of reducing the impact of cyberattacks on UK businesses.

CiSP comprises organizations vetted by NCSC which go through a membership process before being able to join. These members could conduct cybersecurity assessment and penetration testing for NHS organizations, retrospectively assisting in implementing key security controls which may have been overlooked.

They can also help by making sure NHS remote access systems are fully patched and advising on sensible security systems and approved solutions. They can identify critical OT and legacy systems and advise on their security.

The NCSC should continue working with the NHS to enhance provision of public comprehensive guidance on cyber defence and response to potential attack. This would show they are on top of the situation, projecting confidence and reassurance.

It is often said in every crisis lies an opportunity. This is an opportunity for the UK government to show agility in how it deals with cyber threats and how it cooperates with the private sector in creating cyber resilience.

It is an opportunity to lead a much-needed cultural change showing cybersecurity should never be an afterthought.




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Beware Russian and Chinese Positioning for After the Pandemic

9 April 2020

Keir Giles

Senior Consulting Fellow, Russia and Eurasia Programme
Authoritarian regimes can use the COVID-19 crisis to improve their international standing, taking advantage of others’ distraction. Their aims are different, but their methods have much in common.

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An airlifter of the Russian Aerospace Forces prepares to fly to Serbia carrying equipment and professionals during the COVID-19 crisis. Photo by Russian Defence MinistryTASS via Getty Images.

Both Russia and China have mounted combined charm offensives and disinformation campaigns on the back of the pandemic. Shipments of ‘aid’ – reportedly of questionable utility and quality - have gone hand in hand with a concerted effort to deflect any blame from China for the early spread, and an ongoing drive by Russia to undermine states’ confidence and have sanctions lifted.

These concurrent operations have very different objectives, as Russia seeks to subvert international order while China is continuing its bid to demonstrate global leadership - but in both cases, they are seeking long-term gains by exploiting the inattention and distraction of their targets.

Both seek to present themselves as globally responsible stakeholders, but for divergent reasons – especially China which needs the rest of the world to recover and return to stability to ensure its own economic recovery. But despite this, the two campaigns appear superficially similar.

Fertile ground for disinformation

One reason lies in the unique nature of the current crisis. Unlike political issues that are local or regional in nature, COVID-19 affects everybody worldwide. The perceived lack of reliable information about the virus provides fertile ground for information and disinformation campaigns, especially feeding on fear, uncertainty and doubt. But Russia in particular would not be succeeding in its objectives without mis-steps and inattention by Western governments.

Confused reporting on Russia sending medical supplies to the United States showed Moscow taking advantage of a US administration in apparent disarray. Claims Russia was sending ’humanitarian aid’ were only belatedly countered by the US State Department pointing out it had been paid for. Meanwhile the earlier arrival of Russian military equipment in Italy also scored a propaganda victory for Russia, facilitated by curious passivity by the Italian government.

In both cases Russia also achieved secondary objectives. With the United States, Russia scored bonus points by shipping equipment produced by a subsidiary of a company under US sanctions. In the case of Italy, Russian state media made good use of misleading or heavily edited video clips to give the impression of widespread Italian acclaim for Russian aid, combined with disdain for the efforts of the EU.

Beijing’s external information campaigns have sought to deflect or defuse criticism of its early mishandling and misinformation on coronavirus and counter accusations of secrecy and falsifying data while also pursuing an opportunity to exercise soft power. For Moscow, current efforts boost a long-standing and intensive campaign to induce the lifting of sanctions, demonstrating if nothing else that sanctions are indeed an effective measure. Official and unofficial lobbying has intensified in numerous capital cities, and will inevitably find supporters.

But both the aid and the information campaigns are seriously flawed. While appropriate and useful aid for countries that are struggling should of course be welcomed, both Russian and Chinese equipment delivered to Europe has repeatedly been found to be inappropriate or defective

Russian photographs of cardboard boxes stacked loose and unsecured in a transport aircraft bound for the United States sparked alarm and disbelief among military and aviation experts - and there has still been no US statement on what exactly was purchased, and whether it was found to be fit for purpose when it arrived.

Reporting from Italy that the Russian equipment delivered there was ‘80% useless’ has not been contradicted by the Italian authorities. In fact, although the Italian sources criticizing Russia remain anonymous it is striking that - President Trump aside - no government has publicly endorsed materials and assistance received from Russia as actually being useful and helpful.

Even in Serbia, with its traditionally close ties with Russia, the only information forthcoming on the activities of the Russian Nuclear, Biological and Chemical Protection Troops and their equipment that arrived on April 3 was from Russian press releases.

Both countries’ strategic communications efforts are similarly fallible. China’s notoriously heavy-handed approach to its critics is of only limited use in the face of such a severe and immediate threat. One suggestion that the virus originated in the US – an early response to US criticism – has already been walked back by the Chinese diplomat who made it.

And Russia continues to be capable of spectacularly misjudging its targets. When investigative journalists looked more closely at the nature of the assistance to Italy, Russia’s official response was rage and personal threats, laying bare the real nature of the campaign and immediately alienating many of those whom Moscow had sought to win over.

Errors and deficiencies such as these provide opportunities to mitigate the worst side-effects of the campaigns. And actions by individuals can also mitigate much of the impact. The most effective disinformation plays on deeply emotional issues and triggers visceral rather than rational reactions.

Advocates of ’informational distancing’ as well as social distancing suggest a tactical pause to assess information calmly, instead of reacting or spreading it further unthinkingly. This approach would bolster not only calm dispassionate assessment of the real impact of Russian and Chinese actions, but also counter spreading of misinformation on the pandemic as a whole - especially when key sources of disinformation are national leaders seeking to politicize or profit from the crisis.

Limitations of Russian and Chinese altruism must be stated clearly and frankly to fill gaps in public understanding. Where help is genuine, it should of course be welcomed: but if it is the case that assistance received from Moscow or Beijing is not appropriate, not useful, or not fit for purpose, this should be acknowledged publicly.

Even without central direction or coordination with other Russian strategic communications efforts, the self-perpetuating Russian disinformation ecosystem continues to push narratives designed to undermine confidence in institutions and their ability to deal with the crisis. This too must continue to be monitored closely and countered where it matters.

In all cases, miscalculations by Russia or China that expose the true intent of their campaigns – no matter how different their objectives might be - should be watched for closely and highlighted where they occur.

Despite the enormity of the present emergency it is not a time for any government to relax its vigilance over longer-term threats. States must not lose sight of manoeuvres seeking to exploit weakness and distraction. If Russia and China emerge from the current crisis with enhanced authority and unjustifiably restored reputations, this will make it still harder to resist their respective challenges to the current rules-based international order in the future.




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Same Old Politics Will Not Solve Iraq Water Crisis

15 April 2020

Georgia Cooke

Project Manager, Middle East and North Africa Programme

Dr Renad Mansour

Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative

Glada Lahn

Senior Research Fellow, Energy, Environment and Resources Programme
Addressing Iraq’s water crisis should be a priority for any incoming prime minister as it is damaging the country’s attempts to rebuild. But successive governments have allowed the problem to fester.

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Punting in the marshes south of the Iraqi city of Ammarah. Photo by Ghaith Abdul-Ahad/Getty Images.

Historically, Iraq lay claim to one of the most abundant water supplies in the Middle East. But the flow of the Tigris and Euphrates rivers has reduced by up to 40% since the 1970s, due in part to the actions of neighbouring countries, in particular Turkey, upstream.

Rising temperatures and reduced rainfall due to climate change are also negatively impacting Iraq’s water reserves. Evaporation from dams and reservoirs is estimated to lose the country up to 8 billion cubic metres of water every year.

A threat to peace and stability

Shortages have dried up previously fertile land, increasing poverty in agricultural areas. Shortages have also served to fuel conflict: communities faced with successive droughts and government inertia proved to be easy targets for ISIS recruiters, who lured farmers into joining them by offering money and food to feed their families. Economic hardship for those whose livelihoods relied upon river water has also driven rural to urban migration, putting significant strain on already over-populated towns and cities, exacerbating housing, job and electricity shortages, and widening the gap between haves and have-nots.

But scarcity isn’t the most crucial element of Iraq’s water crisis – contamination is. Decades of local government mismanagement, corrupt practices and a lack of regulation of dumping (it is estimated up to 70% of Iraq’s industrial waste is dumped directly into water) has left approximately three in every five citizens without a reliable source of potable water.

In 2018, 118,000 residents of Basra province were hospitalised with symptoms brought on by drinking contaminated water, which not only put a spotlight on the inadequacies of a crumbling healthcare system but sparked mass protests and a subsequent violent crackdown.

The water crisis is also undermining the stability of the country’s federal governance model, by occasionally sparking disputes between Baghdad and the Kurdistan Regional Government, as well as between governorates in the south.

The crisis is both a symptom and a cause of poor governance. Iraq is stuck in a cycle whereby government inaction causes shortages and contamination, which result in economic losses, reduced food supply, increased prices and widespread poor health. This in turn leads to increasing levels of poverty, higher demand on services and civil unrest, increasing the pressure on a weak, dysfunctional system of government.

What can be done?

The first priority should be modernising existing water-management infrastructure - a relic of a time when the problem was an excess rather than a shortage of water (the last time Iraq’s flood defences were required was 1968). Bureaucratic hurdles, widespread corruption and an endless cycle of other crises taking precedent prevent good initiatives from being implemented or scaled up.

Diversifying energy sources to improve provision is crucial. Baghdad has a sewage treatment plant that originally ran on its own electricity source, but this capacity was destroyed in 1991 and was never replaced. The city continues to suffer from dangerous levels of water pollution because the electricity supply from the grid is insufficient to power the plant. Solar energy has great potential in sun-drenched Iraq to bridge the gaping hole in energy provision, but successive governments have chosen to focus on fossil fuels rather than promoting investment to grow the renewables sector.

Heightened tension with upstream Turkey could turn water into another cause of regional conflict. But, if approached differently, collaboration between Iraq and its neighbour could foster regional harmony.

Turkey’s elevated geography and cooler climate mean its water reserves suffer 75% less evaporation than Iraq’s. Given that Turkey’s top energy priority is the diversification of its supply of imported hydrocarbons, a win-win deal could see Turkey exchange access to its water-management infrastructure for delivery of reduced cost energy supplies from Iraq.

German-French cooperation on coal and steel in the 1950s and the evolution of economic integration that followed might provide a model for how bilateral cooperation over one issue could result in cooperation with other regional players (in this case Iran and Syria) on a range of other issues. This kind of model would need to consider the future of energy, whereby oil and gas would be replaced by solar-power exports.

These solutions have been open to policymakers for years and yet they have taken little tangible action. While there are leaders and bureaucrats with the will to act, effective action is invariably blocked by a complex and opaque political system replete with vested interests in maintaining power and wealth via a weak state and limited services from central government.

Breaking the cycle

To break this cycle, Iraq needs a group of professional and able actors outside of government to work with willing elements of the state bureaucracy as a taskforce to pressure for action and accountability. Publishing the recommendations from a hitherto withheld report produced in the aftermath of Basra’s 2018 heath crisis would be a great start.

In time, this taskforce could champion the prioritisation of water on the national agenda, the implementation of infrastructure upgrades, and hold more productive conversations with neighbour states.

With such a high degree of state fragmentation and dysfunction in Iraq, looking to the central government to provide leadership will not yield results. Engagement with a coalition of non-state actors can begin to address the water crisis and also open a dialogue around new models of governance for other critical issues. This might even be a starting point for rewriting the tattered social contract in Iraq.

This piece is based on insights and discussion at a roundtable event, Conflict and the Water Crisis in Iraq, held at Chatham House on March 9 as part of the Iraq Initiative.




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Beyond Lockdown: Africa’s Options for Responding to COVID-19

21 April 2020

Ben Shepherd

Consulting Fellow, Africa Programme

Nina van der Mark

Research Analyst, Global Health Programme
The continent’s enormous diversity means that there will be no one African experience of COVID-19, nor a uniform governmental response. But there are some common challenges across the continent, and a chance to get the response right.

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Dakar after the Interior Ministry announced compulsory wearing of masks in public and private services, shops and transport, under penalty of sanctions. Photo by SEYLLOU/AFP via Getty Images.

African policymakers face a dilemma when it comes to COVID-19. The first hope is to prevent the virus from gaining a foothold at all, and many African states have significant experience of managing infectious disease outbreaks. The establishment of the Africa Centre for Disease Control highlights the hugely increased focus on public health in recent years.

But capacities to track, test and isolate vary wildly, notably between neighbours with porous and poorly controlled borders and, in most cases, sustained national-level disease control is difficult. Initial clusters of COVID-19 cases are already established in many places, but a lack of testing capacity makes it hard to know the full extent of transmission.

It is not obvious what African states should do as a response. Lack of information about COVID-19 means the proportion of asymptomatic or mild cases is not known, still less the ways in which this is influenced by human geography and demographics.

Africa is an overwhelmingly young continent with a median age under 20. But it also faces chronic malnutrition, which may weaken immune responses, and infectious diseases such as malaria, TB and HIV are widespread which could worsen the impact of COVID-19, particularly if treatment for these diseases is interrupted.

Complex and unknown

Ultimately, how all these factors interact with COVID-19 is complex and remains largely unknown. Africa may escape with a relatively light toll. Or it could be hit harder than anywhere else.

What is clear, however, is that cost of simply following the rest of the world into lockdown could be high. Africa is relatively rural but has higher populations living in informal settlements than anywhere in the world. Many live in cramped and overcrowded accommodation without clean water or reliable electricity, making handwashing a challenge and working from home impossible.

And the benefits appear limited. The goal of lockdowns in most places is not to eliminate the virus but to accept the economic and social costs as a price worth paying in order to ‘flatten the curve’ of infection and protect healthcare systems from being overwhelmed. But this logic does not hold when many of Africa’s healthcare systems are barely coping with pre-coronavirus levels of disease.

Africa suffers in comparison to much of the rest of the world in terms of access to quality and affordable healthcare, critical care beds and specialist personnel. For example, in 2017, Nigeria had just 120 ICU beds for a country of 200 million, equating to 0.07 per 100,000 inhabitants compared to 12.5 per 100,000 in Italy and 3.6 per 100,000 in China.

The pandemic’s ruinous economic impacts could also be more acute for Africa than anywhere else. The continent is highly vulnerable to potential drops in output and relies heavily on demand from China and Europe. Many states are already facing sharply falling natural resource revenues, and investment, tourism and remittances will suffer - all on top of a high existing debt burden.

Analysis by the World Bank shows that Africa will likely face its first recession in 25 years, with the continental economy contracting by up to 5.1% in 2020. Africa will have scant financial ammunition to use in the fight against COVID-19 with currencies weakening, food prices rising, local agri-food supply chains disrupted and food imports likely to decrease as well. A food security emergency appears a strong possibility.

So, although several states have imposed national lockdowns and others closed major urban centres, lockdowns are difficult to manage and sustain, especially in places where the daily hustle of the informal sector or subsistence agriculture are the only means of survival and where the state has neither the trust of the population nor the capacity to replace lost earnings or meet basic needs.

Of course, this is not simply a binary choice between lockdown or no lockdown - a range of intermediate options exist, such as some restriction on movement, curfews, shutting places of worship, banning only large gatherings, or closing pubs, schools and borders.

A significant number of African states have so far taken this middle path. This will not prevent the virus from spreading nor, in all probability, be enough to ensure adequate healthcare for all Africans infected with COVID-19. But it may help slow the spread and buy invaluable time for African states and partners to prepare.

How this time is used is therefore of paramount importance. Popular trust in the state is low in many African countries so strategies must empower communities, not alienate them. Africa’s experience of previous epidemics and long traditions of collective resilience and community-based crisis response - which persist in many places – are significant strengths.

The right messages must be carried by the right messengers, and policies - including cash transfers and food distribution - implemented sensitively. If not, or if responses become militarized, public consent is unlikely to be sustained for long.




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Nigeria’s Political Leaders Need to Win Trust to Tackle COVID-19

23 April 2020

Elizabeth Donnelly

Deputy Director, Africa Programme

Idayat Hassan

Director, Centre for Democracy and Development
COVID-19 will require Nigeria's government to rely on already stretched communities and informal institutions. But there is a yawning gap in trust and accountability between citizens and the state in Nigeria – the crisis will force the state to attempt to bridge this divide.

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News stand in Lagos, Nigeria on April 12, 2020. Photo by PIUS UTOMI EKPEI/AFP via Getty Images.

Nigeria is better placed than many to respond to the arrival of the coronavirus disease. In 2014, it successfully contained a deadly Ebola virus outbreak and the country’s current score on the Epidemic Preparedness Index (38.9 per cent) is higher than the African and global averages.

But the outbreak is compounding Nigeria’s numerous pre-existing crises. It was already grappling with a Lassa fever outbreak that has claimed more than one hundred lives in 2020, the aftermath of recession, and conflict and insecurity within its borders.

Effective leadership to build confidence will be vital. However, President Muhammadu Buhari has made few appearances, delivering his first speech on Nigeria’s response more than one month after the country’s first recorded case. And the indefinite suspension of meetings of the Federal Executive Council has raised questions on the efficacy of the response.

Extended lockdown imposed

The recent loss of President Buhari’s steadfast chief of staff Abba Kyari as a result of contracting COVID-19 is a further significant setback for the presidency. But the administration has established a presidential task force to develop a national strategy and an extended lockdown has been imposed on the most affected states  Lagos, Ogun and the Federal Capital Territory of Abuja. The country has also closed national borders and is expanding testing capacity to 1,500 per day.

However, when Nigeria’s first case was recorded on February 27 it was state governments that initially took action  shutting schools, closing state borders and imposing lockdowns. Going forwards, the 36 state governments will have a key role to play although their governance capacity and commitment varies widely.

The federal government has released $2.7 million to support the Nigeria Centre for Disease Control (NCDC), and promised an additional $18 million  but this falls well short of the estimated $330 million needed to tackle the coronavirus disease in Nigeria. The government is looking to its private sector to help make up the difference. The country’s finances are under severe pressure with Nigerian crude oil  the main source of government revenue and foreign exchange reserves  selling for as low as $12 or $13 a barrel (with production costs of around $22 per barrel), and a debt servicing to revenue ratio of more than 50 per cent even before the oil price crash.

Facing its second recession in four years, with -3.4 per cent GDP growth forecast by the IMF, the country has little economic resilience. Nigeria will not be able to sustain restrictions on its 81.15 million-strong workforce, 83.2 per cent of which operate in the informal sector. One area at particular risk is food security, as the pandemic is disrupting farming, supply chains and trade. By building on past benefit programmes, the federal government is providing cash and distributing food to vulnerable households, but this important effort is being hampered by poor communication, inefficiencies and a lack of transparency  longstanding challenges in many aspects of public service delivery in Nigeria.

In the absence of a reliable social safety net, Nigerians trust and rely on their families, communities and the informal economy to see them through difficult times. It is these informal mechanisms that lend Nigeria its oft-referenced resilience, which has enabled society to function and continue while a largely disconnected political class has focused on self-enrichment.

It is through these traditional channels that the government will need to deliver information, support, testing and treatment. But without high levels of trust, the administration may find it difficult to do so. Many Nigerians initially considered the pandemic a hoax, some describing it as a ‘rich man’s disease’, while others see it as another conspiracy by politicians to loot the treasury.

Lockdown measures have also heightened tensions across the country. Some citizens are rebelling and in one instance burned down a police station in response to the closure of mosques in Katsina state. Marking a further breakdown in the relationship between the population and its leaders, the Nigerian National Human Rights Commission (NHRC) recently reported security services enforcing the lockdown have extrajudicially killed 18 people, while, so far, COVID-19 has killed 25 people in Nigeria.

Mitigating the spread and worst consequences of the virus will depend on the state rebuilding trust with its citizens through effective communication and action. It is particularly important that the community mechanisms of support are protected as they come under growing pressure as communities become increasingly affected by the virus.

The stark choice facing most Nigerians  between risking starvation and risking contagion  means a sustained lockdown is not a tenable option. People will choose to go to work. This will especially be the case as people grow weary of measures imposed upon them by a state that the vast majority of the population believe does not serve or care for them.

Having largely ignored the needs of Nigeria’s citizens for decades, the political class face an uphill battle in building trust with the population. Earning this trust is not only crucial for the struggle against COVID-19 but also for Nigeria’s longer-term progress and system of political governance.




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Can Protest Movements in the MENA Region Turn COVID-19 Into an Opportunity for Change?

29 April 2020

Dr Georges Fahmi

Associate Fellow, Middle East and North Africa Programme
The COVID-19 pandemic will not in itself result in political change in the MENA region, that depends on the ability of both governments and protest movements to capitalize on this moment. After all, crises do not change the world - people do.

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An aerial view shows the Lebanese capital Beirut's Martyrs Square that was until recent months the gathering place of anti-government demonstrators, almost deserted during the novel coronavirus crisis, on 26 March 2020. Photo by -/AFP via Getty Images.

COVID-19 has offered regimes in the region the opportunity to end popular protest. The squares of Algiers, Baghdad, and Beirut – all packed with protesters over the past few months – are now empty due to the pandemic, and political gatherings have also been suspended. In Algeria, Iraq and Lebanon, COVID-19 has achieved what snipers, pro-regime propaganda, and even the economic crisis, could not.

Moreover, political regimes have taken advantage of the crisis to expand their control over the political sphere by arresting their opponents, such as in Algeria where the authorities have cracked down on a number of active voices of the Hirak movement. Similarly, in Lebanon, security forces have used the pandemic as an excuse to crush sit-ins held in Martyr’s Square in Beirut and Nour Square in Tripoli.

However, despite the challenges that the pandemic has brought, it also offers opportunities for protest movements in the region. While the crisis has put an end to popular mobilization in the streets, it has  created new forms of activism in the shape of solidarity initiatives to help those affected by its consequences.

In Iraq, for example, protest groups have directed their work towards awareness-raising and sharing essential food to help mitigate the problem of food shortages and rising prices across the country. In Algeria, Hirak activists have run online campaigns to raise awareness about the virus and have encouraged people to stay at home. Others have been cleaning and disinfecting public spaces. These initiatives increase the legitimacy of the protest movement, and if coupled with political messages, could offer these movements an important chance to expand their base of popular support.

Exposes economic vulnerability

Economic grievances, corruption and poor provision of public services have been among the main concerns of this recent wave of protests. This pandemic only further exposes the levels of economic vulnerability in the region. COVID-19 is laying bare the socio-economic inequalities in MENA countries; this is particularly evident in the numbers of people engaged in the informal economy with no access to social security, including health insurance and pensions.

Informal employment, approximately calculated by the share of the labour force not contributing to social security, is estimated to amount to 65.5% of total employment in Lebanon, 64.4% in Iraq, and 63.3% in Algeria. The crisis has underscored the vulnerability of this large percentage of the labour force who have been unable to afford the economic repercussions of following state orders to stay at home.

The situation has also called attention to the vital need for efficient public services and healthcare systems. According to the fifth wave of the Arab Barometer, 74.4% of people in Lebanon are dissatisfied with their country’s healthcare services, as are 67.8% of people in Algeria and 66.5% in Iraq.

Meanwhile, 66.2% of people in Lebanon believe it is necessary to pay a bribe in order to receive better healthcare, as do 56.2% of people in Iraq and 55.9% in Algeria. The COVID-19 crisis has highlighted the need for more government investment in public healthcare systems to render them more efficient and less corrupt, strengthening the protesters’ case for the need for radical socio-economic reforms.

On the geopolitical level, the crisis puts into question the stability-focused approach of Western powers towards the region. For years, Western powers have directed their aid towards security forces in the interests of combating terrorism but COVID-19 has proved itself to be a much more lethal challenge to both the region and the West.

Facing this new challenge requires international actors to reconsider their approach to include supporting health and education initiatives, as well as freedom of expression and transparency. As argued by Western policymakers themselves, it was China’s lack of transparency and slow response that enabled the proliferation of the virus, when it could have been contained in Wuhan back in December 2019.

This crisis therefore offers regional protest movements the opportunity to capitalize on this moment and push back against the policies of Western powers that have invested in regional stability only to the extent of combating Islamic jihad. 

But crises do not change the world, people do. The COVID-19 pandemic will not in itself result in political change in the MENA region. Rather, it brings opportunities and risks that, when exploited, will allow political actors to advance their own agendas. While the crisis has put an end to popular mobilization and allowed regimes to tighten their grip over the political sphere, behind these challenges lie real opportunities for protest movements.

The current situation represents a possibility for them to expand their popular base through solidarity initiatives and has exposed more widely the importance of addressing socio-economic inequalities. Finally, it offers the chance to challenge the stability-focused approach of Western powers towards the region which until now has predominantly focused on combating terrorism.




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WITHDRAWN: Extraordinary apolipoprotein oxidation in chronic hepatitis C and liver cirrhosis [13. Other]

Withdrawn by Author.




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Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic acid programmable protein arrays [11. Microarrays/Combinatorics/Display Technology]

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.




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Multiple hypothesis testing in proteomics: A strategy for experimental work [Invited]

In quantitative proteomics work, the differences in expression of many separate proteins are routinely examined to test for significant differences between treatments. This leads to the multiple hypothesis testing problem: when many separate tests are performed many will be significant by chance and be false positive results. Statistical methods such as the false discovery rate (FDR) method that deal with this problem have been disseminated for more than one decade. However a survey of proteomics journals shows that such tests are not widely implemented in one commonly used technique, quantitative proteomics using two-dimensional electrophoresis (2-DE). We outline a selection of multiple hypothesis testing methods, including some that are well known and some lesser known, and present a simple strategy for their use by the experimental scientist in quantitative proteomics work generally. The strategy focuses on the desirability of simultaneous use of several different methods, the choice and emphasis dependent on research priorities and the results in hand. This approach is demonstrated using case scenarios with experimental and simulated model data.




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Translating Divergent Environmental Stresses into a Common Proteome Response through Hik33 in a Model Cyanobacterium [Research]

The histidine kinase Hik33 plays important roles in mediating cyanobacterial response to divergent types of abiotic stresses including cold, salt, high light (HL), and osmotic stresses. However, how these functions are regulated by Hik33 remains to be addressed. Using a hik33-deficient strain (hik33) of Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found that Hik33 depletion induces differential protein expression highly similar to that induced by divergent types of stresses. This typically includes downregulation of proteins in photosynthesis and carbon assimilation that are necessary for cell propagation, and upregulation of heat shock proteins, chaperons, and proteases that are important for cell survival. This observation indicates that depletion of Hik33 alone mimics divergent types of abiotic stresses, and that Hik33 could be important for preventing abnormal stress response in the normal condition. Moreover, we found the majority of proteins of plasmid origin were significantly upregulated in hik33, though their biological significance remains to be addressed. Together, the systematically characterized Hik33-regulated cyanobacterial proteome, which is largely involved in stress responses, builds the molecular basis for Hik33 as a general regulator of stress responses.




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Proteome and phosphoproteome analysis of brown adipocytes reveals that RICTOR loss dampens global insulin/AKT signaling [Research]

Stimulating brown adipose tissue (BAT) activity represents a promising therapy for overcoming metabolic diseases. mTORC2 is important for regulating BAT metabolism, but its downstream targets have not been fully characterized. In this study, we apply proteomics and phosphoproteomics to investigate the downstream effectors of mTORC2 in brown adipocytes. We compare wild-type controls to isogenic cells with an induced knockout of the mTORC2 subunit RICTOR (Rictor-iKO) by stimulating each with insulin for a 30-minute time course. In Rictor-iKO cells, we identify decreases to the abundance of glycolytic and de novo lipogenesis enzymes, and increases to mitochondrial proteins as well as a set of proteins known to increase upon interferon stimulation. We also observe significant differences to basal phosphorylation due to chronic RICTOR loss including decreased phosphorylation of the lipid droplet protein perilipin-1 in Rictor-iKO cells, suggesting that RICTOR could be involved with regulating basal lipolysis or droplet dynamics. Finally, we observe mild dampening of acute insulin signaling response in Rictor-iKO cells, and a subset of AKT substrates exhibiting statistically significant dependence on RICTOR.




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Modulation of natural HLA-B*27:05 ligandome by ankylosing spondylitis-associated endoplasmic reticulum aminopeptidase 2 (ERAP2) [Research]

The human leucocyte antigen (HLA)-B*27:05 allele and the endoplasmic reticulum-resident aminopeptidases are strongly associated with ankylosing spondylitis (AS), a chronic inflammatory spondyloarthropathy. This study examined the effect of endoplasmic reticulum aminopeptidase 2 (ERAP2) in the generation of the natural HLA-B*27:05 ligandome in live cells. Complexes of HLA-B*27:05-bound peptide pools were isolated from human ERAP2-edited cell clones and the peptides were identified using high throughput mass spectrometry analyses. The relative abundance of thousand ligands was established by quantitative tandem mass spectrometry and bioinformatics analysis. The residue frequencies at different peptide position, identified in presence or absence of ERAP2, determined structural features of ligands and their interactions with specific pockets of antigen binding site of HLA-B*27:05 molecule. Sequence alignment of ligands identified with species of bacteria associated with HLA-B*27-dependent reactive arthritis was performed. In the absence of ERAP2, peptides with N-terminal basic residues, and minority canonical P2 residues are enriched in the natural ligandome. Further, alterations of residue frequencies and hydrophobicity profile at P3, P7, and P positions were detected. In addition, several ERAP2-dependent cellular peptides were highly similar to protein sequences of arthritogenic bacteria, including one human HLA-B*27:05 ligand fully conserved in a protein from Campylobacter jejuni. These findings highlight the pathogenic role of this aminopeptidase in the triggering of AS autoimmune disease.




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Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-Induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses [Research]

Accumulation and propagation of hyperphosphorylated tau (p-tau) is a common neuropathological hallmark associated with neurodegeneration of Alzheimer's disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and related tauopathies. Extracellular vesicles, specifically exosomes, have recently been demonstrated to participate in mediating tau propagation in brain. Exosomes produced by human induced pluripotent stem cell (iPSC)-derived neurons expressing mutant Tau (mTau), containing the P301L and V337M Tau mutations of FTDP-17, possess the ability to propagate p-tau pathology after injection into mouse brain.  To gain an understanding of the mTau exosome cargo involved in tau pathogenesis, these pathogenic exosomes were analyzed by proteomics and bioinformatics. The data showed that mTau expression dysregulates the exosome proteome to result in (1) proteins uniquely present only in mTau, and not control exosomes, (2) the absence of proteins in mTau exosomes, uniquely present in control exosomes, and (3) shared proteins which were significantly up-regulated or down-regulated in mTau compared to control exosomes. Notably, mTau exosomes (not control exosomes) contain ANP32A (also known as I1PP2A), an endogenous inhibitor of the PP2A phosphatase which regulates the phosphorylation state of p-tau.  Several of the mTau exosome-specific proteins have been shown to participate in AD mechanisms involving lysosomes, inflammation, secretases, and related processes.  Furthermore, the mTau exosomes lacked a substantial portion of proteins present in control exosomes involved in pathways of localization, vesicle transport, and protein binding functions. The shared proteins present in both mTau and control exosomes represented exosome functions of vesicle-mediated transport, exocytosis, and secretion processes. These data illustrate mTau as a dynamic regulator of the biogenesis of exosomes to result in acquisition, deletion, and up- or down-regulation of protein cargo to result in pathogenic mTau exosomes capable of in vivo propagation of p-tau neuropathology in mouse brain. 




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Proteomics of Campylobacter jejuni growth in deoxycholate reveals Cj0025c as a cystine transport protein required for wild-type human infection phenotypes [Research]

Campylobacter jejuni is a major cause of food-borne gastroenteritis. Proteomics by label-based two-dimensional liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) identified proteins associated with growth in 0.1% sodium deoxycholate (DOC, a component of gut bile salts), and system-wide validation was performed by data-independent acquisition (DIA-SWATH-MS). LC-MS/MS quantified 1326 proteins (~82% of the predicted C. jejuni proteome), of which 1104 were validated in additional biological replicates by DIA-SWATH-MS. DOC resulted in a profound proteome shift with 512 proteins showing significantly altered abundance. Induced proteins were associated with flagellar motility and antibiotic resistance; and these correlated with increased DOC motility and resistance to polymyxin B and ciprofloxacin. DOC also increased human Caco-2 cell adherence and invasion. Abundances of proteins involved in nutrient transport were altered by DOC and aligned with intracellular changes to their respective carbon sources. DOC increased intracellular levels of sulfur-containing amino acids (cysteine and methionine) and the dipeptide cystine (Cys-Cys), which also correlated with reduced resistance to oxidative stress. A DOC induced transport protein was Cj0025c, which has sequence similarity to bacterial Cys-Cys transporters. Deletion of cj0025c (cj0025c) resulted in proteome changes consistent with sulfur starvation, as well as attenuated invasion, reduced motility, atypical morphology, increased antimicrobial susceptibility and poor biofilm formation. Targeted metabolomics showed cj0025c was capable of utilizing known C. jejuni amino and organic acid substrates commensurate with wild-type. Medium Cys-Cys levels however, were maintained in cj0025c relative to wild-type. A toxic Cys-Cys mimic (selenocystine) inhibited wild-type growth, but not cj0025c. Provision of an alternate sulfur source (2 mM thiosulfate) restored cj0025c motility. Our data confirm that Cj0025c is a Cys-Cys transporter that we have named TcyP consistent with the nomenclature of homologous proteins in other species.




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Perlecan knockdown significantly alters extracellular matrix composition and organization during cartilage development [Research]

Perlecan is a critical proteoglycan found in the extracellular matrix (ECM) of cartilage. In healthy cartilage, perlecan regulates cartilage biomechanics and we previously demonstrated perlecan deficiency leads to reduced cellular and ECM stiffness in vivo. This change in mechanics may lead to the early onset osteoarthritis seen in disorders resulting from perlecan knockdown such as Schwartz-Jampel syndrome (SJS). To identify how perlecan knockdown affects the material properties of developing cartilage, we used imaging and liquid chromatography–tandem mass spectrometry (LC-MS/MS) to study the ECM in a murine model of SJS, Hspg2C1532Y-Neo. Perlecan knockdown led to defective pericellular matrix formation, whereas the abundance of bulk ECM proteins, including many collagens, increased. Post-translational modifications and ultrastructure of collagens were not significantly different; however, LC-MS/MS analysis showed more protein was secreted by Hspg2C1532Y-Neo cartilage in vitro, suggesting that the incorporation of newly synthesized ECM was impaired. In addition, glycosaminoglycan deposition was atypical, which may explain the previously observed decrease in mechanics. Overall, these findings provide insight into the influence of perlecan on functional cartilage assembly and the progression of osteoarthritis in SJS.




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G8 and Russian Foreign Policy: Overcoming Shortcomings

1 June 2008 , Number 6

Dmitri Medvedev’s appearance at the G8 Summit in Hokkaido will be his first step on the wide international stage that Vladimir Putin occupied with such a swagger. Expectations of change will be high, but they are likely to be unrealistic at such an early stage in Medvedev’s presidency. Putin’s foreign policy legacy is a heavy one and he has made it clear that Medvedev will be no soft touch, but will his approach ultimately be more productive?

John Lough

Associate Fellow, Russia and Eurasia Programme




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Moscow's Domestic Policy: Russian Roulette

1 October 2008 , Number 4

Russia’s military action in Georgia was driven by Moscow’s domestic agenda. Foreign policy has become a tool of collective control back home. While the ‘ruling tandem’ has gained popularity, the new consensus does not provide for modernisation. Will the predatory state reform or collapse?

Lilia Shevtsova

Senior Associate, Carnegie Moscow Centre




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Russian Policy on Iran: Trump and Trap

1 February 2007 , Number 1

Russia is playing a risky game in Iran, continuing to build a nuclear power plant while supporting United Nations sanctions on Tehran for its nuclear policy. Moscow may be hoping for a deal with the west, but if restraint fails and Iran goes nuclear, the missiles would be too close for comfort. Equally a pre-emptive American or Israeli strike on Iranian nuclear sites might unleash serious consequences for Russia too.

Yury Fedorov

Associate Fellow, Russia and Eurasia Programme, Chatham House

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An Iranian woman passes by mural paintings of Iran's supreme leader Ayatollah Ali Khamenei (L) and the late founder of Islamic Republic Ayatollah Ruhollah Khomeini (R)




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Nuclear Weapons: Trident is the Answer, Now What was the Question?

1 February 2007 , Number 3

Next month, parliament will vote on whether to replace Britain’s Trident nuclear missile submarines with a new and similar system. There is little doubt the proposal will be approved with support from the Conservative opposition. But the facts used to back the government’s favourite option raise as many questions as answers. The future of Britain’s defence is in doubt.

Andrew Norman

Senior Lecturer, Defence Studies, King's College London

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Trident Submarine USS Georgia




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Politics, policy-making and the presence of images of suffering children

7 May 2020 , Volume 96, Number 3

Helen Berents

In 2017 Trump expressed pity for the ‘beautiful babies’ killed in a gas attack on Khan Shaykhun in Syria before launching airstrikes against President Assad's regime. Images of suffering children in world politics are often used as a synecdoche for a broader conflict or disaster. Injured, suffering, or dead; the ways in which images of children circulate in global public discourse must be critically examined to uncover the assumptions that operate in these environments. This article explores reactions to images of children by representatives and leaders of states to trace the interconnected affective and political dimensions of these images. In contrast to attending to the expected empathetic responses prompted by images of children, this article particularly focuses on when such images prompt bellicose foreign policy decision-making. In doing this, the article forwards a way of thinking about images as contentious affective objects in international relations. The ways in which images of children's bodies and suffering are strategically deployed by politicians deserves closer scrutiny to uncover the visual politics of childhood inherent in these moments of international politics and policy-making.




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Horror, apocalypse and world politics (free)

7 May 2020 , Volume 96, Number 3

Tim Aistrope and Stefanie Fishel

World politics generates a long list of anxiety-inspiring scenarios that threaten to unravel everyday life with sudden and violent destruction. From total war and the concentration camps, through nuclear firestorms, global pandemics and climate disaster, the diabolical violence of the recent past and conceivable future is the stuff of nightmares. Yet International Relations scholars and practitioners are often criticized for being disconnected from the human realities of international calamity. The challenge for both is to engage world politics in a way that foregrounds the human consequences of extreme violence and depravation. In this article, we explore these difficult experiences through popular culture representations of the apocalypse, a subject of intense interest for researchers in a discipline where global destruction is a distinct possibility. However, we take a different route by engaging the apocalypse through the horror genre, the one place where human suffering is explicitly accentuated. We argue that the horror genre is at once an access point for ethical engagement with the human consequences of extreme violence and a complex terrain where dark imaginings can be politically loaded, culturally specific and ethically ambiguous.




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Rethinking youth bulge theory in policy and scholarship: incorporating critical gender analysis

7 May 2020 , Volume 96, Number 3

Lesley Pruitt

For decades ‘youth bulge’ theory has dominated understandings of youth in mainstream International Relations. Youth bulge theory has also become part of some public media analyses, mainstream political rhetoric, and even officially enshrined in the foreign policy of some states. Through the ‘youth bulge’ lens, youth—especially males—have been presented as current or future perpetrators of violence. However, this article argues that the youth bulge thesis postulated in mainstream IR is based on flawed theoretical assumptions. In particular, supporters of youth bulge theory fail to engage with existing research by feminist IR scholars and thus take on a biological essentialist approach. This has led to theoretical and practical misunderstandings of the roles youth play in relation to conflict, peace and security. These partial and biased understandings have also resulted in less effective policy-making. In critically reflecting on the ‘youth bulge’ thesis, this article argues that applying gender analysis is crucial to understanding the involvement of young people in general—and young men in particular—in conflict. Doing so will contribute to advancing more accurate analysis in scholarship and policy-making.




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The multilevel identity politics of the 2019 Eurovision Song Contest

7 May 2020 , Volume 96, Number 3

Galia Press-Barnathan and Naama Lutz

This article uses the 2019 Eurovision Song Contest (ESC) that took place in Tel Aviv to explore how cultural mega-events serve both as political arenas and as tools for identity construction, negotiation and contestation. These processes of identity politics are all conducted across national–subnational–international–transnational levels. The hosting of mega-events fleshes out these multiple processes in a very strong manner. We first discuss the politics of hosting mega-events in general. We then examine the identity politics associated more specifically with the Eurovision Song Contest, before examining in depth the complex forms of identity politics emerging around the competition following the 2018 Israeli victory. We suggest that it is important to study together the multiple processes—domestic, international and transnational—of identity politics that take place around the competition, as they interact with each other. Consequently, we follow the various stakeholders involved at these different levels and their interactions. We examine the internal identity negotiation process in Israel surrounding the event, the critical actors debating how to use the stage to challenge the liberal, western, ‘normal’ identity Israel hoped to project in the contest and how other stakeholders (participating states, national broadcasting agencies, participating artists) reacted to them, and finally we examine the behaviour of the institution in charge, the European Broadcasting Union, and national governments. We contribute to the study of mega-events as fields of contestation, to the understanding of the complex, multilevel nature of national identity construction, negotiation and contestation in the current era, and more broadly to the role that popular culture plays in this context.




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Power and diplomacy in the post-liberal cyberspace

7 May 2020 , Volume 96, Number 3

André Barrinha and Thomas Renard

It is becoming widely accepted that we have transitioned, or are now transitioning, from an international liberal order to a different reality. Whether that reality is different solely in terms of power dynamics, or also in terms of values and institutions, is up for discussion. The growing body of literature on ‘post-liberalism’ is used as an entry-point for this article, which aims to explore how the post-liberal transition applies to cyberspace. We explore how power dynamics are evolving in cyberspace, as well as how established norms, values and institutions are contested. The article then looks at the emergence of cyber diplomacy as a consequence and response to the post-liberal transition. As it will be argued, if cyberspace was a creation of the liberal order, cyber-diplomacy is a post-liberal world practice. What role it plays in shaping a new order or building bridges between different political visions, and what it means for the future of cyberspace, will constitute key points of discussion.




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Violence, visuality and world politics

7 May 2020 , Volume 96, Number 3

In the May 2020 issue of International Affairs, we explore the many uses of images in the conduct of global politics.

Helen Berents and Constance Duncombe

This special section brings together diverse spaces and modes of visuality through specific, sustained attention to the various types of violence depicted. In doing so, these articles draw out a concern for the visual constitution of violence in global politics, and its emotional and political consequences. Individually and collectively, the contributions highlight the ways in which policy-makers and researchers are daily confronted by violent images that influence how complex political problems are seen and consequently understood. Paying attention to the power of the visuality of violence is necessary to understand how certain kinds of policy responses to direct and indirect violence unfold.




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Corporate Raiding in Russia, Ukraine and Kazakhstan

Invitation Only Research Event

5 November 2019 - 9:00am to 1:00pm

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

Event participants

John Patton, Argentem Creek
Rachel Cook, Peters & Peters
Tom Mayne, University of Exeter
Olga Bischof, Brown Rudnick LLP
Isobel Koshiw, Global Witness
Anton Moiseienko, RUSI

The widespread practice of illicit acquisition of a business or part of a business in the former Soviet states, known as ‘reiderstvo’ or asset-grabbing, is a major risk that disincentivises investment in the region.

It is distinct from the way corporate raiding occurs in the West and enabled by factors such as corruption and weak protection of property rights.

This roundtable will assess the practice of corporate raiding in Russia, Ukraine and Kazakhstan: its evolution over time, knock-on effects and potential solutions. The speakers will also address the implications for the UK legal system and possible policy responses.

Event attributes

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Department/project

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Political Will Was Not Enough for Justice Reform in Moldova

27 November 2019

Cristina Gherasimov

Former Academy Associate, Russia and Eurasia Programme
The pro-reform Sandu government had the will to dismantle oligarchic power structures, but was taken down by limited political experience.

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Maia Sandu in Germany in July. Photo: Getty Images.

The lack of political will to carry out rule of law reforms is frequently the reason why reforms are not fully implemented. The case of Moldova proves that in societies where strong vested interests still persist, political savviness is equally as important as political will.

Old and new political power brokers in Moldova struck a fragile pact in June to oust Vladimir Plahotniuc. Plahotniuc had built a network of corruption and patronage with the help of the Democratic Party, which he treated as a personal vehicle and which allowed him and a small economic elite circle to enrich themselves off of government institutions and state-owned enterprises, to the detriment of Moldovan citizens and the health of their political process.

Maia Sandu, co-leader of the pro-reform ACUM electoral bloc, then formed a technocratic government with a remit to implement Moldova’s lagging reform agenda. Though made up of ministers with the integrity and political will to implement difficult transformational reforms, its biggest weakness was its coalition partner – the pro-Russian Socialists’ Party and its informal leader, Igor Dodon, the president of Moldova.

Now the Socialists – threatened by how key reforms to the justice system would impact their interests – have joined forces with Plahotniuc’s former allies, the Democratic Party, to oust ACUM, exploiting the party’s lack of political savviness. 

Reform interrupted

It was always clear the coalition would be short-lived. President Dodon and the co-ruling Socialists joined to buy themselves time, with the hope that they could restrict the most far-reaching reforms and tie the hands of ACUM ministers. In less than five months, however, the Sandu government initiated key reforms in the judicial system, aimed at dismantling Plahotniuc’s networks of patronage but also impacting the Socialists, who to a large degree also profited from the previous status quo.

The red line came over a last-minute change in the selection process of the prosecutor general proposed by Sandu on 6 November, which the Socialists claimed was unconstitutional and gave them the justification to put forward a motion of no confidence in the Sandu government. This was conveniently supported by the Democratic Party, who appeared threatened by an independent prosecutor’s office and saw an opportunity to return to power.

Thus, the political will to reform proved insufficient in the absence of a clear strategy on how to address the concerns of the old regime that they would be prosecuted and their vested interests threatened. Here, ACUM’s lack of political experience let them down. With their hands tied from the beginning in a fragile coalition with the Socialists, ACUM were unable to prevent sabotage from within state institutions and their own coalition, and could not find consensus to proceed with more radical methods to tackle corruption.

Less than two days after the Sandu government was out, a new government was sworn in on 14 November. Prime Minister Ion Chicu was an adviser to President Dodon before taking office and former minister of finance under the Plahotniuc-backed government of Pavel Filip, as part of a cabinet of ministers consisting largely of other presidential advisers and former high-level bureaucrats and ministers from the Plahotniuc era. 

The new government

A top priority for the Chicu government is to convince the international community that it is independent from President Dodon, and that its ‘technocrats’ will keep the course of reforms of the Sandu government. This is critical to preserving the financial assistance of Western partners, which the Moldovan government heavily relies on, particularly with a presidential election campaign next year, when they will likely want to create fiscal space for various giveaways to voters.

But within its first week in office, Chicu appears incapable of walking this line. Reverting to the initially proposed pre-selection process of prosecutor general signals that the post could be filled by a loyal appointee of President Dodon. Moreover, Chicu’s first visit abroad was to Russia, allegedly a major financial contributor of the Socialists’ Party. With the Socialists now holding the presidency, government, Chisinau mayoralty, and the parliament speaker’s seat, the danger of an increased Russian influence on key political decisions is very real.

A government steered by President Dodon risks bringing Moldova back to where it was before June, with a political elite mimicking reforms while misusing power for private gains. The biggest danger is that instead of continuing the reform process to bring Moldova back on its European integration path, the new government may focus on strengthening the old patronage system, this time with President Dodon at the top of the pyramid.

Lessons

This new minority government, supported by the Democrats, is a more natural one for President Dodon and therefore has more chances to survive, at least until presidential elections in autumn of 2020. Both the Socialists and the Democrats will likely seek to use this time to rebuild their own methods of capturing state resources. But with the Socialists relying on the Democrats’ votes in parliament, this is a recipe for further political instability.

Similar to Moldova, several other states across the post-Soviet space such as Ukraine and Armenia have had new political forces come to power with the political will and mandate to carry out difficult reforms to strengthen rule of law and fight systemic corruption in their countries. What they all have in common is the lack of political experience of how to create change, while old elites, used to thinking on their feet to defend their vested interests, retain their connections and economic and political influence.

Moldova is a good example of why political will needs to be backed up by clear strategy on how to deal with threatened vested interests in order for new political forces to be able to maintain themselves in power and reforms to be sustainable. When the chance comes again for fresh leaders to come to power, it is importantthey are politically prepared to use it swiftly and wisely.




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Russian Economic Policy and the Russian Economic System: Stability Versus Growth

17 December 2019

How is it possible for the directors of the Russian economy to pursue an orthodox stabilization policy with a great measure of success and yet to have achieved so little to stem the growth slowdown? This paper examines the reasons for the divergence in economic management.

Professor Philip Hanson OBE

Former Associate Fellow, Russia and Eurasia Programme

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Bank of Russia Governor Elvira Nabiullina, Economic Development Minister Maxim Oreshkin, Deputy Prime Minister Vitaly Mutko, Labour and Social Safety Minister Maxim Topilin, Economy and Finance Department Head Valery Sidorenko, and Russian presidential aide Andrei Belousov (l–r) after a meeting on stimulating economic growth, at Gorki residence, Moscow, on 8 October 2019. Photo: Getty Images.

Summary

  • Russia’s economic management is currently praised for its achievement of macroeconomic stability. Inflation has been brought down; the budget is in surplus; national debt is low; and the reserves are ample. At the same time, there is much criticism of the failure at present to secure more than very slow economic growth.
  • The macro-stabilization of 2014–18 was of a conventional, ‘liberal’ kind. Public spending was cut, and a budget rule was introduced that (so far) has weakened the link between increases in oil prices and increases in budgetary expenditure. The austerity campaign was harsh. Pensioners, the military, regional budgets and business all lost out, but in reality put up little resistance. The austerity drive was facilitated by the autocratic nature of the regime.
  • The growth slowdown dates from 2012, and cannot simply be blamed on falls in the oil price and sanctions. Rapid growth in 1999–2008 consisted in large part of recovery from the deep recession of the 1990s and the initial development of a services sector. These sources of growth are no longer available; investment is low; and the labour force is declining. The Western world also has a slow growth problem, but at a higher level of per capita output. In Russia, private investment and competition are inhibited by an intrusive and corrupt state. If the rule of law were in place, the economy would perform better in the long run. That would require a profound reform of formal and informal institutions.
  • The leadership wants faster growth, but has powerful incentives not to embark on systemic reform. Even the pragmatic ministers of the ‘economic bloc’ of government, who understand the problem, share this interest in maintaining the status quo. Growth is thus being sought through a highly ambitious programme, in 2018–24, of ‘national projects’, state-led and largely state-financed. This is already running into difficulties.
  • The contrast between successful stabilization and a (so far) unsuccessful growth strategy illustrates the difference between policymaking within a given system and reform of that system. Systemic reform brings with it more potential unintended consequences than do changes in policy. In the case of Russia, movement towards a rule of law could destabilize the social and political system. It is therefore unlikely to be attempted.




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The New Orthodox Church of Ukraine: Opportunities and Challenges of Canonical Independence

Invitation Only Research Event

22 January 2020 - 10:00am to 11:30am

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

Event participants

Archbishop Yevstraty (Zoria) of Chernihiv, Deputy Head of Department for External Church Relations, Ukrainian Orthodox Church (Orthodox Church of Ukraine)

In January 2019, the Ecumenical Patriarchate of Constantinople granted the Orthodox Church of Ukraine a self-governing status, ending its centuries-long subordination to the Moscow Patriarchate. The Russian Orthodox Church condemned this decision and severed its links with the Constantinople Patriarchate.

More than 500 parishes have left the Ukrainian Orthodox Church of the Moscow Patriarchate to join the newly independent Ukrainian Orthodox Church (UOC).

What challenges is the new church facing? Has its independence been recognized by other Orthodox churches? How is it affected by the schism between Constantinople and Moscow? What are UOC’s priorities in relations with the West and with the Orthodox world?

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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How Putin Tries to Depoliticize Russia’s Youth

7 January 2020

Professor Nikolai Petrov

Senior Research Fellow, Russia and Eurasia Programme, Chatham House

Ekaterina Aleynikova

Independent Analyst
Vladimir Putin’s condescending remarks on Greta Thunberg’s activism say more about the Kremlin’s attitude towards Russian youth than climate change.

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Vladimir Putin meets with representatives of the Russian Student Brigades in the Kremlin. Photo: Getty Images.

Climate change debates have not taken root in Russia. Yet, while speaking at an energy forum in Moscow, Vladimir Putin chose to comment on Greta Thunberg, the prominent 16-year-old Swedish eco-activist. Adopting his usual sarcastically condescending persona, Putin expressed regret that the ‘kind’ and ‘very sincere’ girl was being used by adults for their own political interests in such a ‘cruel, emotional way’.

These remarks may appear to have been intended to dismiss Thunberg’s environmental concerns. However, among the Russian public, concern about climate change is not widespread.

Fridays for Future, the movement started by Thunberg, received little uptake in Russia, inspiring less than 100 people to take to the streets in September. This does not compare to the 50,000 or more people who came out to protest unfair elections and police brutality in Moscow in August. Indeed, Thunberg herself is largely perceived negatively among the Russian public.

Thus, there was no need for Putin to warn his domestic audience about Thunberg’s ‘mistaken’ cause. In fact, Putin’s key message was not to aimed at the young activist or even the climate change debate. Although presented as spontaneous, his words revealed a carefully-constructed narrative. It was expressed in general terms.

‘Adults must do everything not to bring teenagers and children into extreme situations,’ Putin urged, ‘when somebody uses children and teenagers in their own interests, it only deserves to be condemned.’ In fact, these statements were targeted at delegitimizing any sort of political engagement from young people.

Those familiar with Kremlin propaganda would have recognized this narrative from the statements that have been made about Alexey Navalny’s supporters over the recent years, who have been portrayed as ‘naïve’ and ‘manipulated’. According to the state, young people should be apolitical, and hence any involvement they have in politics must come as a result of manipulation by ‘ill-intended’ adults.

The same attitude is exploited to impose restrictions on individual freedoms, as is the case with the infamous gay propaganda law, which disguises discrimination in the language of protecting children. Portraying the youth as innately dependent legitimizes paternalistic interventions from the state, defining the norms of conduct.

This narrative is part of a wider strategy employed by the Russian government to promote political apathy among the country’s youth. There have been efforts to discourage young people from participating in political protests, such as warnings of expulsion at schools and universities and threats of fines and prosecution against parents whose children attend demonstrations.

A vivid illustration of these efforts is the recent conviction of Yegor Zhukov, a 21-year-old student from Moscow’s Higher School of Economics who discussed regime change on his blog. Instead of the four years in prison for extremism that the prosecutor asked for, he was sentenced to three years of probation, with a prohibition against him posting online as a condition. His sentencing sends a message, to Zhukov and to all young people interested in politics – he is free to go perhaps, but not free to speak out.

It is not all ‘stick’ in the government’s approach to young people. There is also some ‘carrot’. The Kremlin has been paying close attention to the youth ever since the protests of 2011–12, which demonstrated conclusively that growing up under Putin has not prevented young people from imagining alternatives to his regime. Since then, Putin has made a habit of regular meetings with young people, and a number of initiatives have been rolled out to select and reward ‘top performers’.

Through presidential grants, such as the Sirius educational programme in Sochi, the government selects and trains high-achieving students in STEM subjects. This is done under the umbrella of promoting technological innovation.

Thus, there exist clear boundaries over where creative thinking is allowed: it is encouraged in technical sciences, but not in social sciences or humanities. To the ‘right’ type of talented children participating in government programmes, the ‘wrong’ image of Zhukov stands as a stark contrast.

For the majority of young people, Russia’s education system does not support the development of independent, critical thinking. In 2016, Putin personally endorsed an initiative to create a single official history textbook that excludes ‘internal contradictions and double interpretations’. This demonstrates the desire of the regime to promote convergent thinking among the wider population.

This strategy towards Russia’s youth reflects the fears of Putin’s regime, which sees young people as having disruptive potential. There have been false dawns for Russia’s liberal opposition before (most recently in 2012) and, while the summer’s protests were significant, it remains unclear whether the new generation really are more progressive than those who went before.

Nevertheless, dissatisfaction with the status quo is apparent among Russia’s youth. They do not see Russia offering them good opportunities. Over 50% of those aged 18–24 reported that they want to emigrate, in a recent survey by Levada Center. Whether this discontent provides the impetus for political change in Russia may depend on the success of the Kremlin’s efforts to depoliticize Russia’s youth.




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Three Challenges for UK Peacebuilding Policy in the South Caucasus After Brexit

21 January 2020

Laurence Broers

Associate Fellow, Russia and Eurasia Programme
Building on the legacies of a long-term British investment in a peace strategy for the South Caucasus is a realistic and attainable goal.

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A building in Nagorny Karabakh flies the flag of the self-proclaimed republic. 'Abkhazia, South Ossetia and Nagorny Karabakh have evolved into examples of what scholars call "de facto states" that, to differing degrees, control territory, provide governance and exercise internal sovereignty,' writes Laurence Broers. Photo: Getty Images.

What does Britain’s departure from the EU mean for the country’s policy towards the South Caucasus, a small region on the periphery of Europe, fractured by conflict? Although Britain is not directly involved in any of the region’s peace processes (except in the case of the Geneva International Discussions on conflicts involving Georgia, as an EU member state), it has been a significant stakeholder in South Caucasian stability since the mid-1990s.

Most obviously, Britain has been the single largest foreign investor in Caspian oil and gas. Yet beyond pipelines, Britain also has been a significant investor in long-term civil society-led strategies to build peace in the South Caucasus.

Through what was then the Global Conflict Prevention Pool, in the early 2000s the Department for International Development (DfID) pioneered large-scale peacebuilding interventions, such as the Consortium Initiative, addressing Armenian-Azerbaijani conflict, in 2003-09. These built civic networks in the South Caucasus and partnerships with British-based NGOs.

This experience left a strong intellectual legacy. British expertise on the South Caucasus, including specific expertise on its conflicts, is highly regarded in the region and across the world.

There is also a strong tradition of British scholarship on the Caucasus, and several British universities offer Caucasus-related courses. Through schemes such as the John Smith Fellowship Trust, the Robert Bosch Stiftung Academy Fellowship at Chatham House and Chevening Scholarships, significant numbers of young leaders from the South Caucasus have spent time in British institutions and built effective relationships within them.

Three challenges

This niche as a champion of long-term, strategic peacebuilding and repository of area-specific knowledge should not be lost as Britain’s relationship with the EU and regional actors evolves. This can be ensured through awareness of three challenges confronting a post-Brexit Caucasus policy.

The first challenge for London is to avoid framing a regional policy in the South Caucasus as an extension of a wider ‘Russia policy’. Deteriorating Russian-British relations in recent years strengthen a tendency to view policies in the European neighbourhood through the traditional prisms of Cold War and Russian-Western rivalries.

Yet an overwhelming focus on Russia fails to capture other important aspects of political developments in South Caucasus conflicts. Although often referred to as ‘breakaway’ or ‘occupied’ territories, Abkhazia, South Ossetia and Nagorny Karabakh are not ungoverned spaces. They have evolved into examples of what scholars call ‘de facto states’ that, to differing degrees, control territory, provide governance and exercise internal sovereignty.

Few disagree that these entities would not survive without external patronage. But neither does that patronage explain their sustainability on its own. Russia-centricity diminishes Britain’s latitude to engage on the full range of local drivers sustaining these entities, contributing instead to less effective policies predicated on competition and containment.

A second and related challenge is to maintain and develop Britain’s position on the issue of engaging populations in these entities. De facto states appear to stand outside of the international rules-based system. Yet in many cases, their civil societies are peopled by skilled and motivated activists who want their leaders to be held accountable according to international rules.

Strategies of isolation ignore these voices and contribute instead to fearful and demoralized communities less likely to engage in a transformation of adversarial relationships. Making this case with the wider international community, and facilitating the funding of local civil societies in contested territories, would be important steps in sustaining an effective British policy on the resolution of conflicts.    

The third challenge for Britain is to maintain a long-term approach to the conflicts of the South Caucasus alongside potential short-term imperatives in other policy fields, as relationships shift post-Brexit.

In this fluid international environment, the Foreign and Commonwealth Office has a role to play both as an internal champion of a long-term peacebuilding strategy and a coordinator of British efforts with those of multilateral actors engaged in the South Caucasus. These include the United Nations, the EU’s Special Representative for the South Caucasus and the Crisis in Georgia and OSCE’s Special Representative for the OSCE Chairperson-in-Office for the South Caucasus, all of which have built relationships with relevant actors on the ground.

Recommendations

Britain’s niche as a champion and advocate of a strategic approach to peaceful change can be secured post-Brexit in the following ways.  

First, in-house expertise is crucial to effective peacebuilding programming. The Foreign Office’s research analysts play a vital role in generating independent internal advice and liaising with academic and NGO communities. Their role could be supplemented by the reinstatement of a regional conflict adviser post, based in Tbilisi, tasked with strengthening Britain’s regional presence on conflict issues and coordinating policy at a regional level.

This post, with a remit to cover conflicts and build up area knowledge and relationships can contribute significantly to working closely with local civil societies, where so much expertise and knowledge resides, as well as other stakeholders.

Second, programming should build in conflict sensitivity by dissociating eligibility from contested political status. This can encourage local populations to take advantage of opportunities for funding, study, comparative learning and professional development irrespective of the status of the entity where they reside.

The Chevening Scholarships are an excellent example, whereby applicants can select ‘South Caucasus’ as their affiliated identity from a drop-down menu. This enables citizens from across the region to apply irrespective of the status of the territory in which they live.   

Finally, a holistic understanding of peace is crucial. Programming in unrecognized or partially-recognized entities should acknowledge that effective peacebuilding needs to embrace political dynamics and processes beyond cross-conflict contact and confidence building. Local actors in such entities may find peacebuilding funding streams defined exclusively in terms of cross-conflict contact more politically risky and ineffective in addressing domestic blockages to peace.

While cross-conflict dynamics remain critical, ‘single-community’ programming framed in terms of civic participation, inclusion, civil society capacity-building, minority and human rights in contested territories, and building the confidence from within to engage in constructive dialogue, are no less important.

The ’global Britain’ promised by Brexit remains a fanciful idea. Quiet, painstaking work to build on the legacies of a long-term British investment in a peace strategy for the South Caucasus, on the other hand, is a realistic and attainable goal.




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POSTPONED: Transitional Justice in Ukraine: What Might it Look Like?

Invitation Only Research Event

17 March 2020 - 9:30am to 1:00pm

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

Event participants

Kirsty Brimelow QC, Barrister, Doughty Street Chambers
Miles Jackson, Associate Professor of Law, University of Oxford
Anton Korynevych, Representative of the President of Ukraine for Crimea
Oleksandra Matviychuk, Head of the Board, Centre for Civil Liberties
Taras Tsymbrivksyy, Head, USAID Human Rights in Action Program; Ukrainian Helsinki Human Rights Union

Still grappling with the war in the east and the occupation of Crimea, Ukraine’s new leadership has announced its intention to develop its transitional justice infrastructure to respond to the human rights violations arising from Russia’s aggression. 

Numerous reports (not least ones by the UN Human Rights Monitoring Mission in Ukraine) list persecutions, illegal detentions, enforced disappearances, torture and killings among the crimes perpetrated in Crimea and parts of occupied Donbas. 

As Ukraine has only just started developing its transitional justice roadmap, this event will seek to discuss viable initial approaches, such as a ‘truth-telling commission’ or amnesties. 

The panellists will also discuss the role for civil society and those directly affected by hostilities in the transitional justice process.  

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Event attributes

Chatham House Rule

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Beware Russian and Chinese Positioning for After the Pandemic

9 April 2020

Keir Giles

Senior Consulting Fellow, Russia and Eurasia Programme
Authoritarian regimes can use the COVID-19 crisis to improve their international standing, taking advantage of others’ distraction. Their aims are different, but their methods have much in common.

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An airlifter of the Russian Aerospace Forces prepares to fly to Serbia carrying equipment and professionals during the COVID-19 crisis. Photo by Russian Defence MinistryTASS via Getty Images.

Both Russia and China have mounted combined charm offensives and disinformation campaigns on the back of the pandemic. Shipments of ‘aid’ – reportedly of questionable utility and quality - have gone hand in hand with a concerted effort to deflect any blame from China for the early spread, and an ongoing drive by Russia to undermine states’ confidence and have sanctions lifted.

These concurrent operations have very different objectives, as Russia seeks to subvert international order while China is continuing its bid to demonstrate global leadership - but in both cases, they are seeking long-term gains by exploiting the inattention and distraction of their targets.

Both seek to present themselves as globally responsible stakeholders, but for divergent reasons – especially China which needs the rest of the world to recover and return to stability to ensure its own economic recovery. But despite this, the two campaigns appear superficially similar.

Fertile ground for disinformation

One reason lies in the unique nature of the current crisis. Unlike political issues that are local or regional in nature, COVID-19 affects everybody worldwide. The perceived lack of reliable information about the virus provides fertile ground for information and disinformation campaigns, especially feeding on fear, uncertainty and doubt. But Russia in particular would not be succeeding in its objectives without mis-steps and inattention by Western governments.

Confused reporting on Russia sending medical supplies to the United States showed Moscow taking advantage of a US administration in apparent disarray. Claims Russia was sending ’humanitarian aid’ were only belatedly countered by the US State Department pointing out it had been paid for. Meanwhile the earlier arrival of Russian military equipment in Italy also scored a propaganda victory for Russia, facilitated by curious passivity by the Italian government.

In both cases Russia also achieved secondary objectives. With the United States, Russia scored bonus points by shipping equipment produced by a subsidiary of a company under US sanctions. In the case of Italy, Russian state media made good use of misleading or heavily edited video clips to give the impression of widespread Italian acclaim for Russian aid, combined with disdain for the efforts of the EU.

Beijing’s external information campaigns have sought to deflect or defuse criticism of its early mishandling and misinformation on coronavirus and counter accusations of secrecy and falsifying data while also pursuing an opportunity to exercise soft power. For Moscow, current efforts boost a long-standing and intensive campaign to induce the lifting of sanctions, demonstrating if nothing else that sanctions are indeed an effective measure. Official and unofficial lobbying has intensified in numerous capital cities, and will inevitably find supporters.

But both the aid and the information campaigns are seriously flawed. While appropriate and useful aid for countries that are struggling should of course be welcomed, both Russian and Chinese equipment delivered to Europe has repeatedly been found to be inappropriate or defective

Russian photographs of cardboard boxes stacked loose and unsecured in a transport aircraft bound for the United States sparked alarm and disbelief among military and aviation experts - and there has still been no US statement on what exactly was purchased, and whether it was found to be fit for purpose when it arrived.

Reporting from Italy that the Russian equipment delivered there was ‘80% useless’ has not been contradicted by the Italian authorities. In fact, although the Italian sources criticizing Russia remain anonymous it is striking that - President Trump aside - no government has publicly endorsed materials and assistance received from Russia as actually being useful and helpful.

Even in Serbia, with its traditionally close ties with Russia, the only information forthcoming on the activities of the Russian Nuclear, Biological and Chemical Protection Troops and their equipment that arrived on April 3 was from Russian press releases.

Both countries’ strategic communications efforts are similarly fallible. China’s notoriously heavy-handed approach to its critics is of only limited use in the face of such a severe and immediate threat. One suggestion that the virus originated in the US – an early response to US criticism – has already been walked back by the Chinese diplomat who made it.

And Russia continues to be capable of spectacularly misjudging its targets. When investigative journalists looked more closely at the nature of the assistance to Italy, Russia’s official response was rage and personal threats, laying bare the real nature of the campaign and immediately alienating many of those whom Moscow had sought to win over.

Errors and deficiencies such as these provide opportunities to mitigate the worst side-effects of the campaigns. And actions by individuals can also mitigate much of the impact. The most effective disinformation plays on deeply emotional issues and triggers visceral rather than rational reactions.

Advocates of ’informational distancing’ as well as social distancing suggest a tactical pause to assess information calmly, instead of reacting or spreading it further unthinkingly. This approach would bolster not only calm dispassionate assessment of the real impact of Russian and Chinese actions, but also counter spreading of misinformation on the pandemic as a whole - especially when key sources of disinformation are national leaders seeking to politicize or profit from the crisis.

Limitations of Russian and Chinese altruism must be stated clearly and frankly to fill gaps in public understanding. Where help is genuine, it should of course be welcomed: but if it is the case that assistance received from Moscow or Beijing is not appropriate, not useful, or not fit for purpose, this should be acknowledged publicly.

Even without central direction or coordination with other Russian strategic communications efforts, the self-perpetuating Russian disinformation ecosystem continues to push narratives designed to undermine confidence in institutions and their ability to deal with the crisis. This too must continue to be monitored closely and countered where it matters.

In all cases, miscalculations by Russia or China that expose the true intent of their campaigns – no matter how different their objectives might be - should be watched for closely and highlighted where they occur.

Despite the enormity of the present emergency it is not a time for any government to relax its vigilance over longer-term threats. States must not lose sight of manoeuvres seeking to exploit weakness and distraction. If Russia and China emerge from the current crisis with enhanced authority and unjustifiably restored reputations, this will make it still harder to resist their respective challenges to the current rules-based international order in the future.




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Webinar: Russian Disinformation's Golden Moment: Challenges and Responses in the COVID-19 Era

Invitation Only Research Event

7 May 2020 - 3:00pm to 4:30pm

Event participants

Anneli Ahonen, Head, StratCom East Task Force, European External Action Service
Keir Giles, Senior Consulting Fellow, Russia and Eurasia Programme, Chatham House
Thomas Kent, Adjunct Associate Professor, Harriman Institute, Columbia University; Senior Fellow, the Jamestown Foundation
Chairs:
James Nixey, Programme Director, Russia and Eurasia, Chatham House
Glen Howard, President, The Jamestown Foundation
The COVID-19 pandemic provides the ideal environment for malign influence to thrive as it feeds on fear and a vacuum of authoritative information. What are the current challenges posed by Russian disinformation, and how should Western nations be responding?
 
In this discussion, jointly hosted by the Jamestown Foundation and the Chatham House Russia and Eurasia Programme, the speakers will consider what best practice looks like in safeguarding Western societies against the pernicious effects of disinformation. 
 
This event will be held on the record.

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Functional recombinant apolipoprotein A5 that is stable at high concentrations at physiological pH [Methods]

APOA5 is a low-abundance exchangeable apolipoprotein that plays critical roles in human triglyceride (TG) metabolism. Indeed, aberrations in the plasma concentration or structure of APOA5 are linked to hypertriglyceridemia, hyperchylomicronemia, myocardial infarction risk, obesity, and coronary artery disease. While it has been successfully produced at low yield in bacteria, the resulting protein had limitations for structure-function studies due to its low solubility under physiological buffer conditions. We hypothesized that the yield and solubility of recombinant APOA5 could be increased by: i) engineering a fusion protein construct in a codon optimized expression vector, ii) optimizing an efficient refolding protocol, and iii) screening buffer systems at physiological pH. The result was a high-yield (25 mg/l) bacterial expression system that produces lipid-free APOA5 soluble at concentrations of up to 10 mg/ml at a pH of 7.8 in bicarbonate buffers. Physical characterization of lipid-free APOA5 indicated that it exists as an array of multimers in solution, and far UV circular dichroism analyses show differences in total α-helicity between acidic and neutral pH buffering conditions. The protein was functional in that it bound and emulsified multilamellar dimyristoyl-phosphatidylcholine vesicles and could inhibit postprandial plasma TG accumulation when injected into C57BL/6J mice orally gavaged with Intralipid.




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Endocytosis of very low-density lipoproteins: an unexpected mechanism for lipid acquisition by breast cancer cells [Research Articles]

We previously described the expression of CD36 and LPL by breast cancer (BC) cells and tissues and the growth-promoting effect of VLDL observed only in the presence of LPL. We now report a model in which LPL is bound to a heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the VLDL receptor to internalize VLDLs via receptor-mediated endocytosis. We also demonstrate that gene-expression programs for lipid synthesis versus uptake respond robustly to triglyceride-rich lipoprotein availability. The literature emphasizes de novo FA synthesis and exogenous free FA uptake using CD36 as paramount mechanisms for lipid acquisition by cancer cells. We find that the uptake of intact lipoproteins is also an important mechanism for lipid acquisition and that the relative reliance on lipid synthesis versus uptake varies among BC cell lines and in response to VLDL availability. This metabolic plasticity has important implications for the development of therapies aimed at the lipid dependence of many types of cancer, in that the inhibition of FA synthesis may elicit compensatory upregulation of lipid uptake. Moreover, the mechanism that we have elucidated provides a direct connection between dietary fat and tumor biology.­.




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A nematode sterol C4{alpha}-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity [Research Articles]

Primitive sterol evolution plays an important role in fossil record interpretation and offers potential therapeutic avenues for human disease resulting from nematode infections. Recognizing that C4-methyl stenol products [8(14)-lophenol] can be synthesized in bacteria while C4-methyl stanol products (dinosterol) can be synthesized in dinoflagellates and preserved as sterane biomarkers in ancient sedimentary rock is key to eukaryotic sterol evolution. In this regard, nematodes have been proposed to convert dietary cholesterol to 8(14)-lophenol by a secondary metabolism pathway that could involve sterol C4 methylation analogous to the C2 methylation of hopanoids (radicle-type mechanism) or C24 methylation of sterols (carbocation-type mechanism). Here, we characterized dichotomous cholesterol metabolic pathways in Caenorhabditis elegans that generate 3-oxo sterol intermediates in separate paths to lophanol (4-methyl stanol) and 8(14)-lophenol (4-methyl stenol). We uncovered alternate C3-sterol oxidation and 7 desaturation steps that regulate sterol flux from which branching metabolite networks arise, while lophanol/8(14)-lophenol formation is shown to be dependent on a sterol C4α-methyltransferse (4-SMT) that requires 3-oxo sterol substrates and catalyzes a newly discovered 3-keto-enol tautomerism mechanism linked to S-adenosyl-l-methionine-dependent methylation. Alignment-specific substrate-binding domains similarly conserved in 4-SMT and 24-SMT enzymes, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of methyl sterols. The combination of these results provides evolutionary leads to sterol diversity and points to cryptic C4-methyl steroidogenic pathways of targeted convergence that mediate lineage-specific adaptations.­­




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Lipid droplet-associated kinase STK25 regulates peroxisomal activity and metabolic stress response in steatotic liver [Research Articles]

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are emerging as leading causes of liver disease worldwide and have been recognized as one of the major unmet medical needs of the 21st century. Our recent translational studies in mouse models, human cell lines, and well-characterized patient cohorts have identified serine/threonine kinase (STK)25 as a protein that coats intrahepatocellular lipid droplets (LDs) and critically regulates liver lipid homeostasis and progression of NAFLD/NASH. Here, we studied the mechanism-of-action of STK25 in steatotic liver by relative quantification of the hepatic LD-associated phosphoproteome from high-fat diet-fed Stk25 knockout mice compared with their wild-type littermates. We observed a total of 131 proteins and 60 phosphoproteins that were differentially represented in STK25-deficient livers. Most notably, a number of proteins involved in peroxisomal function, ubiquitination-mediated proteolysis, and antioxidant defense were coordinately regulated in Stk25–/– versus wild-type livers. We confirmed attenuated peroxisomal biogenesis and protection against oxidative and ER stress in STK25-deficient human liver cells, demonstrating the hepatocyte-autonomous manner of STK25’s action. In summary, our results suggest that regulation of peroxisomal function and metabolic stress response may be important molecular mechanisms by which STK25 controls the development and progression of NAFLD/NASH.




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Macrophage polarization is linked to Ca2+-independent phospholipase A2{beta}-derived lipids and cross-cell signaling in mice [Research Articles]

Phospholipases A2 (PLA2s) catalyze hydrolysis of the sn-2 substituent from glycerophospholipids to yield a free fatty acid (i.e., arachidonic acid), which can be metabolized to pro- or anti-inflammatory eicosanoids. Macrophages modulate inflammatory responses and are affected by Ca2+-independent phospholipase A2 (PLA2)β (iPLA2β). Here, we assessed the link between iPLA2β-derived lipids (iDLs) and macrophage polarization. Macrophages from WT and KO (iPLA2β–/–) mice were classically M1 pro-inflammatory phenotype activated or alternatively M2 anti-inflammatory phenotype activated, and eicosanoid production was determined by ultra-performance LC ESI-MS/MS. As a genotypic control, we performed similar analyses on macrophages from RIP.iPLA2β.Tg mice with selective iPLA2β overexpression in β-cells. Compared with WT, generation of select pro-inflammatory prostaglandins (PGs) was lower in iPLA2β–/–, and that of a specialized pro-resolving lipid mediator (SPM), resolvin D2, was higher; both changes are consistent with the M2 phenotype. Conversely, macrophages from RIP.iPLA2β.Tg mice exhibited an opposite landscape, one associated with the M1 phenotype: namely, increased production of pro-inflammatory eicosanoids (6-keto PGF1α, PGE2, leukotriene B4) and decreased ability to generate resolvin D2. These changes were not linked with secretory PLA2 or cytosolic PLA2α or with leakage of the transgene. Thus, we report previously unidentified links between select iPLA2β-derived eicosanoids, an SPM, and macrophage polarization. Importantly, our findings reveal for the first time that β-cell iPLA2β-derived signaling can predispose macrophage responses. These findings suggest that iDLs play critical roles in macrophage polarization, and we posit that they could be targeted therapeutically to counter inflammation-based disorders.




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Separation of postprandial lipoproteins: improved purification of chylomicrons using an ApoB100 immunoaffinity method [Methods]

Elevated levels of triglyceride-rich lipoproteins (TRLs), both fasting and postprandial, are associated with increased risk for atherosclerosis. However, guidelines for treatment are defined solely by fasting lipid levels, even though postprandial lipids may be more informative. In the postprandial state, circulating lipids consist of dietary fat transported from the intestine in chylomicrons (CMs; containing ApoB48) and fat transported from the liver in VLDL (containing ApoB100). Research into the roles of endogenous versus dietary fat has been hindered because of the difficulty in separating these particles by ultracentrifugation. CM fractions have considerable contamination from VLDL (purity, 10%). To separate CMs from VLDL, we produced polyclonal antibodies against ApoB100 and generated immunoaffinity columns. TRLs isolated by ultracentrifugation of plasma were applied to these columns, and highly purified CMs were collected (purity, 90–94%). Overall eight healthy unmedicated adult volunteers (BMI, 27.2 ± 1.4 kg/m2; fasting triacylglycerol, 102.6 ± 19.5 mg/dl) participated in a feeding study, which contained an oral stable-isotope tracer (1-13C acetate). We then used this technique on plasma samples freshly collected during an 8 h human feeding study from a subset of four subjects. We analyzed fractionated lipoproteins by Western blot, isolated and derivatized triacylglycerols, and calculated fractional de novo lipogenesis. The results demonstrated effective separation of postprandial lipoproteins and substantially improved purity compared with ultracentrifugation protocols, using the immunoaffinity method. This method can be used to better delineate the role of dietary sugar and fat on postprandial lipids in cardiovascular risk and explore the potential role of CM remnants in atherosclerosis.




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High density lipoprotein and its apolipoprotein-defined subspecies and risk of dementia [Patient-Oriented and Epidemiological Research]

Whether HDL is associated with dementia risk is unclear. In addition to apoA1, other apolipoproteins are found in HDL, creating subspecies of HDL that may have distinct metabolic properties. We measured apoA1, apoC3, and apoJ levels in plasma and apoA1 levels in HDL that contains or lacks apoE, apoJ, or apoC3 using a modified sandwich ELISA in a case-cohort study nested within the Ginkgo Evaluation of Memory Study. We included 995 randomly selected participants and 521 participants who developed dementia during a mean of 5.1 years of follow-up. The level of total apoA1 was not significantly related to dementia risk, regardless of the coexistence of apoC3, apoJ, or apoE. Higher levels of total plasma apoC3 were associated with better cognitive function at baseline (difference in Modified Mini-Mental State Examination scores tertile 3 vs. tertile 1: 0.60; 95% CI: 0.23, 0.98) and a lower dementia risk (adjusted hazard ratio tertile 3 vs. tertile 1: 0.73; 95% CI: 0.55, 0.96). Plasma concentrations of apoA1 in HDL and its apolipoprotein-defined subspecies were not associated with cognitive function at baseline or with the risk of dementia during follow-up. Similar studies in other populations are required to better understand the association between apoC3 and Alzheimer’s disease pathology.




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Nonsynonymous SNPs in LPA homologous to plasminogen deficiency mutants represent novel null apo(a) alleles [Patient-Oriented and Epidemiological Research]

Plasma lipoprotein (a) [Lp(a)] levels are largely determined by variation in the LPA gene, which codes for apo(a). Genome-wide association studies (GWASs) have identified nonsynonymous variants in LPA that associate with low Lp(a) levels, although their effect on apo(a) function is unknown. We investigated two such variants, R990Q and R1771C, which were present in four null Lp(a) individuals, for structural and functional effects. Sequence alignments showed the R990 and R1771 residues to be highly conserved and homologous to each other and to residues associated with plasminogen deficiency. Structural modeling showed both residues to make several polar contacts with neighboring residues that would be ablated on substitution. Recombinant expression of the WT and R1771C apo(a) in liver and kidney cells showed an abundance of an immature form for both apo(a) proteins. A mature form of apo(a) was only seen with the WT protein. Imaging of the recombinant apo(a) proteins in conjunction with markers of the secretory pathway indicated a poor transit of R1771C into the Golgi. Furthermore, the R1771C mutant displayed a glycosylation pattern consistent with ER, but not Golgi, glycosylation. We conclude that R1771 and the equivalent R990 residue facilitate correct folding of the apo(a) kringle structure and mutations at these positions prevent the proper folding required for full maturation and secretion. To our knowledge, this is the first example of nonsynonymous variants in LPA being causative of a null Lp(a) phenotype.




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Deficiency in ZMPSTE24 and resulting farnesyl-prelamin A accumulation only modestly affect mouse adipose tissue stores [Research Articles]

Zinc metallopeptidase STE24 (ZMPSTE24) is essential for the conversion of farnesyl–prelamin A to mature lamin A, a key component of the nuclear lamina. In the absence of ZMPSTE24, farnesyl–prelamin A accumulates in the nucleus and exerts toxicity, causing a variety of disease phenotypes. By ~4 months of age, both male and female Zmpste24–/– mice manifest a near-complete loss of adipose tissue, but it has never been clear whether this phenotype is a direct consequence of farnesyl–prelamin A toxicity in adipocytes. To address this question, we generated a conditional knockout Zmpste24 allele and used it to create adipocyte-specific Zmpste24–knockout mice. To boost farnesyl–prelamin A levels, we bred in the "prelamin A–only" Lmna allele. Gene expression, immunoblotting, and immunohistochemistry experiments revealed that adipose tissue in these mice had decreased Zmpste24 expression along with strikingly increased accumulation of prelamin A. In male mice, Zmpste24 deficiency in adipocytes was accompanied by modest changes in adipose stores (an 11% decrease in body weight, a 23% decrease in body fat mass, and significantly smaller gonadal and inguinal white adipose depots). No changes in adipose stores were detected in female mice, likely because prelamin A expression in adipose tissue is lower in female mice. Zmpste24 deficiency in adipocytes did not alter the number of macrophages in adipose tissue, nor did it alter plasma levels of glucose, triglycerides, or fatty acids. We conclude that ZMPSTE24 deficiency in adipocytes, and the accompanying accumulation of farnesyl–prelamin A, reduces adipose tissue stores, but only modestly and only in male mice.




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Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi [Research Articles]

Angiopoietin-like protein 3 (ANGPTL3) inhibits lipid clearance and is a promising target for managing cardiovascular disease. Here we investigated the effects of a high-sugar (high-fructose) diet on circulating ANGPTL3 concentrations in rhesus macaques. Plasma ANGPTL3 concentrations increased ~30% to 40% after 1 and 3 months of a high-fructose diet (both P < 0.001 vs. baseline). During fructose-induced metabolic dysregulation, plasma ANGPTL3 concentrations were positively correlated with circulating indices of insulin resistance [assessed with fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR)], hypertriglyceridemia, adiposity (assessed as leptin), and systemic inflammation [C-reactive peptide (CRP)] and negatively correlated with plasma levels of the insulin-sensitizing hormone adropin. Multiple regression analyses identified a strong association between circulating APOC3 and ANGPTL3 concentrations. Higher baseline plasma levels of both ANGPTL3 and APOC3 were associated with an increased risk for fructose-induced insulin resistance. Fish oil previously shown to prevent insulin resistance and hypertriglyceridemia in this model prevented increases of ANGPTL3 without affecting systemic inflammation (increased plasma CRP and interleukin-6 concentrations). ANGPTL3 RNAi lowered plasma concentrations of ANGPTL3, triglycerides (TGs), VLDL-C, APOC3, and APOE. These decreases were consistent with a reduced risk of atherosclerosis. In summary, dietary sugar-induced increases of circulating ANGPTL3 concentrations after metabolic dysregulation correlated positively with leptin levels, HOMA-IR, and dyslipidemia. Targeting ANGPTL3 expression with RNAi inhibited dyslipidemia by lowering plasma TGs, VLDL-C, APOC3, and APOE levels in rhesus macaques.




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Alirocumab, evinacumab, and atorvastatin triple therapy regresses plaque lesions and improves lesion composition in mice [Research Articles]

Atherosclerosis-related CVD causes nearly 20 million deaths annually. Most patients are treated after plaques develop, so therapies must regress existing lesions. Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab, monoclonal antibodies against cholesterol-regulating proprotein convertase subtilisin/kexin type 9 and angiopoietin-like protein 3, may provide more benefit. We investigated the effect of such lipid-lowering interventions on atherosclerosis in APOE*3-Leiden.CETP mice, a well-established model for hyperlipidemia. Mice were fed a Western-type diet for 13 weeks and thereafter matched into a baseline group (euthanized at 13 weeks) and five groups that received diet alone (control) or with treatment [atorvastatin; atorvastatin and alirocumab; atorvastatin and evinacumab; or atorvastatin, alirocumab, and evinacumab (triple therapy)] for 25 weeks. We measured effects on cholesterol levels, plaque composition and morphology, monocyte adherence, and macrophage proliferation. All interventions reduced plasma total cholesterol (37% with atorvastatin to 80% with triple treatment; all P < 0.001). Triple treatment decreased non-HDL-C to 1.0 mmol/l (91% difference from control; P < 0.001). Atorvastatin reduced atherosclerosis progression by 28% versus control (P < 0.001); double treatment completely blocked progression and diminished lesion severity. Triple treatment regressed lesion size versus baseline in the thoracic aorta by 50% and the aortic root by 36% (both P < 0.05 vs. baseline), decreased macrophage accumulation through reduced proliferation, and abated lesion severity. Thus, high-intensive cholesterol-lowering triple treatment targeting all apoB-containing lipoproteins regresses atherosclerotic lesion area and improves lesion composition in mice, making it a promising potential approach for treating atherosclerosis.