me Scholarship and the ship of state: rethinking the Anglo-American strategic decline analogy By feedproxy.google.com Published On :: Thu, 12 Mar 2015 11:44:46 +0000 12 March 2015 , Volume 91, Number 2 Katherine C. Epstein Full Article
me Implementing the NATO Wales Summit: From Strategy to Action By feedproxy.google.com Published On :: Mon, 16 Mar 2015 11:00:01 +0000 Invitation Only Research Event 26 February 2015 - 1:00pm to 27 February 2015 - 5:00pm German Institute for International and Security Affairs, Berlin, Germany Meeting Summarypdf | 80.56 KB Event participants Xenia Wickett, Project Director, US; Dean, The Queen Elizabeth II Academy for Leadership in International Affairs, Chatham HouseDr Christian Moelling, International Security Division Associate, SWP-Berlin The NATO Summit, held in September 2014 in Newport, Wales, was a waypoint in the larger strategic vision for NATO over the coming decade. As the alliance continues to confront challenges on its eastern and southern frontiers, it must find ways to adapt its strategy for more effective responses, while also staying ahead of emerging threats and risks. The event will bring together senior representatives from a number of the NATO member states, NATO partners and external experts from industry, the media and the think-tank and academic communities, to examine what NATO member states have done thus far to move the deliverables forward, and how to most effectively work together in continuing to do so. Attendance at this event is by invitation only.This is the second of two workshops held in collaboration with SWP-Berlin; the first took place at Chatham House in October 2014. Event attributes External event Department/project US and the Americas Programme, NATO: Charting the Way Forward Full Article
me Allies Beware: Americans Support a More Limited Role for the US By feedproxy.google.com Published On :: Wed, 11 May 2016 12:45:03 +0000 12 May 2016 Bruce Stokes Associate Fellow, US and the Americas Programme (based in the US) @bruceestokes Xenia Wickett Former Head, US and the Americas Programme; Former Dean, The Queen Elizabeth II Academy for Leadership in International Affairs @xeniawickett LinkedIn While not as isolationist or unilateralist as some campaign rhetoric might suggest, new polling shows the American public broadly supports less engagement with the rest of the world. 2016-05-11-US-Philippines.jpg US military personnel take part in joint military exercises with the Philippines, Australia and Japan in Crow Valley on 14 April 2016. Photo by Getty Images. While the American election cycle could be perceived as an occasionally amusing distraction, the rise of new factions and sentiments among the electorate will have an impact not just in America’s domestic politics but also with respect to its role in the world. Recent polling by the Pew Research Center shows clearly the desire among many Americans for a different international engagement for the US, one that could have significant implications for America’s allies.PollingTo date, the campaign rhetoric of both the Republican and Democratic contenders for the White House has raised questions about America’s continuing global commitment.But what does the public think? The Pew Research Center has recently released its periodic survey of how Americans view America’s place in the world. The results suggest that stereotypes of Americans’ isolationism or protectionism do not capture the nuance in public sentiment. Wariness of international engagement coexists with assertiveness on some issues and a belief that the US is a force for good in the world. And these views often divide along partisan lines and between generations.A majority of Americans (57%) think the U.S. should deal with its own problems and let other countries deal with theirs as best they can, a sentiment that has increased from 46% in 2010. Moreover, roughly two-thirds say ‘we should not think so much in international terms but concentrate more on our own national problems’. In part this may be the case because a plurality of Americans thinks the United States does too much (41% too much, 27% too little) in helping solve world problems.The fact that six-in-ten Americans believe that problems in the world would be even worse without US involvement will not reassure many non-Americans who care deeply about how and where the US is engaged, not just that it is.American isolationism is a partisan affair. Republicans (62%) are far more likely than Democrats (47%) to voice the view that the US should deal with its own problems. Notably, about two-thirds of registered Republicans or Republican-leaning independents who favour Donald Trump (68%) express such isolationist sentiments, as do more than half of the Democratic backers of Sen. Bernie Sanders (54%). At the same time, over half of registered Democrats and Democratic-leaning independents who favour Hillary Clinton (52%) believe the US should help other countries deal with their problems.The US has often been seen by its allies as acting in a unilateralist fashion, but the polling is more nuanced than this. About half (51%) believe that the US should take into account the views of its major allies when deciding its foreign policies. However, of more concern for America’s allies (and potentially adversaries), roughly four-in-ten (42%) believe Washington should go it alone in international matters.Despite Trump’s criticisms, 53% of the American public holds a positive view of NATO and 77% voice the view that US membership in the security alliance has been a good thing for the United States.In addition to some wariness with regards to engaging internationally in security arenas, Americans are also generally wary of global economic engagement – protectionist sentiment is rising. Only 44% believe such US involvement is a good thing; more (49%) say such engagement is bad, lowering wages and costing jobs. These views also differ along partisan lines with more on the right than left thinking US involvement in the world economy has been a bad thing. Trump supporters are even more against economic globalization.Rising scepticismThe results do not show an unambiguous move towards more American isolationism or unilateralism. But the trends broadly show that the American public is moving towards, as President Obama put it in 2012, a focus on ‘nation building at home’. It should come as no surprise – President Obama has presided over a period in which the US has increasingly limited its extraterritorial ambitions to those that more directly affect its vital national interests. It is therefore worth noting that this more limited engagement is one that is, broadly, supported by the public on both sides of the aisle.There are, as have been noted, partisan differences. But the next president will govern over all Americans not just those from their own party. They will have to function in the context of an American public, the majority of whom wants the US to deal with its own problems, letting other countries manage as best they can. While who becomes president clearly matters – they have the capacity to lead their populations in certain directions - the rising scepticism among many Americans for investing in the globalized world will resonate regardless of who takes office.The implications for America’s allies are significant. For those issues that are not directly of concern to the United States, longstanding partners are going to have to find ways to manage on their own or with less American support. And even on those issues that are of direct national interest, they might find the US less sensitive to their interests and concerns. This could hold true not just in the realm of security but on economic issues also – if America becomes more protectionist, others will surely follow. Many of America’s allies have perceived the United States to be an unreliable ally in recent years. Asian partners, such as Japan and South Korea, have started to take more responsibility for their own security and are working to build additional partnerships with neighbours. European allies have been, at times, disappointed by what they perceive to be a less engaged America, such as in Libya and Syria. If the next president follows the public majority, these allies will need to get used to this new role for the United States.This article has been published jointly with Real Clear World.To comment on this article, please contact Chatham House Feedback Full Article
me Does Brexit Mean the Future Is President Trump? By feedproxy.google.com Published On :: Thu, 21 Jul 2016 12:57:03 +0000 21 July 2016 Dr Jacob Parakilas Former Deputy Head, US and the Americas Programme Xenia Wickett Former Head, US and the Americas Programme; Former Dean, The Queen Elizabeth II Academy for Leadership in International Affairs @xeniawickett LinkedIn The growing anti-establishment backlash on both sides of the Atlantic may not swing November’s election, but the world has fundamentally changed. 2016-07-21-TrumpRNC.jpg Donald Trump enters the stage on the first day of the 2016 Republican National Convention. Photo by Getty Images. The British vote to leave the EU is (and should be) seen as a wakeup call for political elites on both sides of the Atlantic. Under normal circumstances, the institutional support that crossed party lines for the Remain campaign should have ensured it a comfortable victory; instead, it lost by a not-insignificant 52−48 per cent margin. Similarly, Donald Trump has alienated the establishment of both American parties – while Democratic dislike is predictable, the extent of the Republican elite’s discomfort with Trump, clearly on display at the party’s convention in Cleveland this week, is extremely unusual at this point in an election campaign which is more typically a display of ‘rally around the candidate’. But as Brexit demonstrated, the conventional logic may not apply in 2016.There are significant differences between the UK referendum and the US elections. Some of this is structural – a national referendum operates along very different lines than a US presidential election, after all, and the US electorate is much larger and more diverse than its British equivalent. Furthermore, American voters will be making a choice between individuals as well as ideas. This does not necessarily work to the advantage of either Donald Trump or Hillary Clinton (both of whom have the highest unfavourability ratings for presidential candidates seen in decades), but highly individualized questions of personality and temperament will impact voter behaviour in a way that they did not for British referendum voters. Finally, who wins the US election will depend in very large part on state politics and electoral college math – as the 2000 election showed, the candidate who wins the popular vote does not necessarily end up as president.But there is a far more important message that politicians in the US, UK and, more broadly, Europe, should take away from the Brexit result. Regardless of what happens in the US elections, elites no longer necessarily hold the preponderance of power. The disenfranchised who have historically either not had the mass or the coherence to communicate it now do - at least on occasion.This is not an ideological split – Brexit voters came together from all parts of the political spectrum. Equally, in the US, Sanders and Trump voters are bucking the system in both the Democratic and Republican parties.There is a significant backlash under way in both countries towards aspects of globalization, going beyond the traditional right/left divide. Allowing for some differences in specifics, the American and British political establishments have, over the past few decades, broadly eased restrictions on the free movement of capital, goods and people across national borders. There have been notable benefits associated with this approach that have mostly been distributed inclusively, but the costs have typically hit those already less advantaged and without opportunities or skills to mitigate them. Those who have been left out or left behind from these changes are discovering their own political power.Politicians are going to have to find ways not just to appeal to these voters who feel disenfranchised by existing structures, but also address their legitimate concerns. There will of course be partisan policy solutions put forward on both sides. But inevitably the political leadership is going to have to find ways to bridge party lines to realize solutions to those social and economic inequalities. Ignoring them, as many have in the past, is increasingly a quick path to losing power.Unless the world wants to turn back to more isolationist and protectionist times, with the slower growth and inequalities that this includes, politicians are also going to have to do a better job of explaining the benefits of globalization. And, more importantly, they will have to ensure that these benefits reach their broader population more equitably and that the costs are better mitigated. So the Brexit vote does not necessarily presage a Trump victory on 8 November, but it shows in stark terms that the world has fundamentally changed – the time when elites alone could call the shots is gone. Politicians, including Hillary Clinton, will need to respond proactively to the causes of the dissatisfaction rather than waiting until the next time they need the public vote.To comment on this article, please contact Chatham House Feedback Full Article
me Institutionalization, path dependence and the persistence of the Anglo- American special relationship By feedproxy.google.com Published On :: Fri, 26 Aug 2016 10:57:44 +0000 1 September 2016 , Volume 92, Number 5 Ruike Xu Full Article
me A Transatlantic Strategy for 2020: The Political Dimension By feedproxy.google.com Published On :: Wed, 05 Apr 2017 12:04:00 +0000 Invitation Only Research Event 2 May 2017 - 12:00pm to 1:15pm Chatham House, London Event participants Dr Robin Niblett CMG, Director, Chatham HouseChair: Xenia Wickett, Head, US and the Americas Programme and Dean, Queen Elizabeth II Academy for Leadership in International Affairs, Chatham House The transatlantic partnership has provided the backbone to the liberal international order ever since the end of the Second World War. The tumultuous political events of 2016 denote a brutal rupture from the dominant global position of the transatlantic partnership and threaten to undermine the partnership itself. Only by understanding that the current problems facing the transatlantic relationship have deep structural roots will it be possible to find ways to prevent further erosion, sustain the benefits of the existing partnership and build opportunities for transatlantic cooperation in the future. Ahead of the publication of his new paper, Robin Niblett, will join us to share his thoughts on the challenges, opportunities and potential strategies towards securing the future of the transatlantic relationship. Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project US and the Americas Programme Courtney Rice Senior Programme Manager, US and the Americas Programme (0)20 7389 3298 Email Full Article
me England and Australia Are Failing in Their Commitments to Refugee Health By feedproxy.google.com Published On :: Mon, 09 Sep 2019 12:50:31 +0000 10 September 2019 Alexandra Squires McCarthy Former Programme Coordinator, Global Health Programme Robert Verrecchia Both boast of universal health care but are neglecting the most vulnerable. 2019-09-09-Manus.jpg A room where refugees were once housed on Manus Island, Papua New Guinea. Photo: Getty Images. England and Australia are considered standard-bearers of universal access to health services, with the former’s National Health Service (NHS) recognized as a global brand and the latter’s Medicare seen as a leader in the Asia-Pacific region. However, through the exclusion of migrant and refugee groups, each is failing to deliver true universality in their health services. These exclusions breach both their own national policies and of international commitments they have made.While the marginalization of mobile populations is not a new phenomenon, in recent years there has been a global increase in anti-migrant rhetoric, and such health care exclusions reflect a global trend in which undocumented migrants, refugees and asylum seekers are denied rights.They are also increasingly excluded in the interpretation of phrases such as ‘leave no one behind’ and ‘universal health coverage’, commonly used by UN bodies and member states, despite explicit language in UN declarations that commits countries to include mobile groups.Giving all people – including undocumented migrants and asylum seekers – access to health care is essential not just for the health of the migrant groups but also the public health of the populations that host them. In a world with almost one billion people on the move, failing to take account of such mobility leaves services ill-equipped and will result in missed early and preventative treatment, an increased burden on services and a susceptibility to the spread of infectious disease.EnglandWhile in the three other nations of the UK, the health services are accountable to the devolved government, the central UK government is responsible for the NHS in England, where there are considerably greater restrictions in access.Undocumented migrants and refused asylum seekers are entitled to access all health care services if doctors deem it clinically urgent or immediately necessary to provide it. However, the Home Office’s ‘hostile environment’ policies towards undocumented migrants, implemented aggressively and without training for clinical staff, are leading to the inappropriate denial of urgent and clearly necessary care.One example is the case of Elfreda Spencer, whose treatment for myeloma was delayed for one year, allowing the disease to progress, resulting in her death.In England, these policies, which closely link health care and immigration enforcement, are also deterring people from seeking health care they are entitled to. For example, medical bills received by migrants contain threats to inform immigration enforcement of their details if balances are not cleared in a certain timeframe. Of particular concern, the NGO Maternity Action has demonstrated that such a link to immigration officials results in the deterrence of pregnant women from seeking care during their pregnancy.Almost all leading medical organizations in the United Kingdom have raised concerns about these policies, highlighting the negative impact on public health and the lack of financial justification for their implementation. Many have highlighted that undocument migrants use just and estimated 0.3% of the NHS budget and have pointed to international evidence that suggests that restrictive health care policies may cost the system more.AustraliaIn Australia, all people who seek refuge by boat are held, and have their cases processed offshore in Papua New Guinea (PNG) and Nauru, at a cost of almost A$5 billion between 2013 and 2017. Through this international agreement, in place since 2013, Australia has committed to arrange and pay for the care for the refugees, including health services ‘to a standard of care broadly comparable to that available to the general Australian community under the public health system’.However, the standard of care made available to the refugees is far from comparable to that available to the general population in Australia. Findings against the current care provision contractor on PNG, Pacific International Hospital, which took over in the last year, are particularly damning.For instance, an Australian coroner investigating the 2014 death from a treatable leg infection of an asylum seeker held in PNG concluded that the contractor lacked ‘necessary clinical skills’, and provided ‘inadequate’ care. The coroner’s report, issued in 2018, found the company had also, in other cases, denied care, withheld pain relief, distributed expired medication and had generally poor standards of care, with broken or missing equipment and medication, and services often closed when they were supposed to be open.This has also been reiterated by the Royal Australasian College of Physicians, which has appealed to the Australian government to end its policies of offshore processing immediately, due to health implications for asylum seekers. This echoes concerns of the medical community around the government’s ongoing attempts to repeal the ‘Medivac’ legislation, which enables emergency medical evacuation from PNG and Nauru.Bad policyBoth governments have signed up to UN Sustainable Development Goals commitment to ‘safe and orderly migration’, an essential component of which is access to health care. The vision for this was laid out in a global action plan on promoting the health of refugees and migrants, agreed by member states at the 2019 World Health Assembly.However, rather than allow national policies to be informed by such international plans and the evidence put forward by leading health professionals and medical organizations, the unsubstantiated framing of migrants as a security risk and economic burden has curtailed migrant and refugee access to health care.The inclusion of migrants and refugees within universal access to health services is not merely a matter of human rights. Despite being framed as a financial burden, ensuring access for all people may reduce costs on health services through prevention of costly later-stage medical complications, increased transmission of infections and inefficient administrative costs of determining eligibility.Thailand provides an example of a middle-income country that recognized this, successfully including all migrants and refugees in its health reforms in 2002. Alongside entitling all residents to join the universal coverage scheme, the country also ensured that services were ‘migrant friendly’, including through the provision of translators. A key justification for the approach was the economic benefit of ensuring a healthy migrant population, including the undocumented population.The denial of quality health services to refugees and undocumented migrants is a poor policy choice. Governments may find it tempting to gain political capital through excluding these groups, but providing adequate access to health services is part of both governments’ commitments made at the national and international levels. Not only are inclusive health services feasible to implement and good for the health of migrants and refugees, in the long term, they are safer for public health and may save money. Full Article
me America's Coronavirus Response Is Shaped By Its Federal Structure By feedproxy.google.com Published On :: Mon, 16 Mar 2020 09:00:36 +0000 16 March 2020 Dr Leslie Vinjamuri Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme @londonvinjamuri Google Scholar The apparent capacity of centralized state authority to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. 2020-03-16-Coronavirus-America.jpg 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 responseFor 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 oversightIn 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. Full Article
me Coronavirus: All Citizens Need an Income Support By feedproxy.google.com Published On :: Mon, 16 Mar 2020 10:50:49 +0000 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. 2020-03-16-coronavirus-delivery.jpg 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 moneyBoth 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. Full Article
me The G20’s Pandemic Moment By feedproxy.google.com Published On :: Tue, 24 Mar 2020 16:57:35 +0000 24 March 2020 Jim O'Neill Chair, Chatham House The planned emergency meeting of the G20 leaders could be the beginning of smart, thoughtful, collective steps to get beyond this challenging moment in history. 2020-03-24-COVID-Vaccine A researcher works on a vaccine against coronavirus COVID-19 at the Copenhagen University research lab. Photo by THIBAULT SAVARY/AFP via Getty Images. Having chaired the independent (and global) Antimicrobial Resistance (AMR) Review for David Cameron, I know a similar approach should have been taken quickly about COVID-19.Similar not in precise nature but - in so far as incorporating infectious disease modelling, and using economic analysis to try to contain and solve it - it should be applied in parallel.The AMR Review is well-known for highlighting the potential loss of life as well as the economic costs of an escalating growth of resistance to antimicrobials, and the inaction to prevent it.In particular we showed that, by 2050, there could be around 10 million people each year dying from AMR, and an accumulated $100trn economic cost to the world from 2015 to 2050.Horrendous outcomesWhat is less focused on, as we showed in our final report, is that to prevent these horrendous outcomes, a 'mere' $42bn would need to be invested globally. This would give an investment return of something like 2,000%.I shudder to think what policymakers could do if we don’t make these investments and we reach a situation - possibly accelerated itself by escalating the inappropriate use of antibiotics in this COVID-19 crisis - where we run out of useful antibiotics. It will be a much longer time period to find new vaccines to beat COVID-19.In addition to this crisis, requiring G20 policymakers to back up their generous words about combatting AMR would mean they need to spend around $10bn instigating the generally agreed Market Incentive Awards to promote serious efforts by pharmaceutical companies.In fact, given that the financial crisis we are also now in means companies are greatly dependent on our governments for their future survival, perhaps the pharma Industry will finally understand the real world concept of 'Pay or Play', where companies that don’t try to find new antibiotics are taxed to provide the pool of money for others that are bold enough to try. And realise there is a world coming of different risk-rewards for all, including them.When applied to the COVID-19 challenge, it is useful to look at the required investment in accelerating as much as possible the efforts to find useful vaccines to beat it, but also to immediately introduce the therapeutics and diagnostics in countries that are so poorly prepared.Those Asian countries affected early include a number that seem to have coped so far in keeping the crisis to a minimum because they had the appropriate therapeutics and diagnostics, despite not having vaccines. A sum of approximately $10 bn from the G20 would be sufficient to cover all these vital areas.Now consider the economics of social distancing. As soon as it became apparent that our policymakers were heeding the Chinese method of trying to suppress COVID-19, it was immediately obvious that our economies would - at least for a short period - sustain the collapse of GDP that China self-imposed in February. From industrial production and other regular monthly data, the Chinese economy has declined by around 20%.It is quite likely many other economies - probably each of the G7 countries - will experience something not too dissimilar in March. And, to stop our complex democracies from further immediate pressure including social disharmony, governments in many countries have needed to undertake dramatic unconventional steps.Here in the UK, our new chancellor effectively had three budgets within less than a fortnight. And outside of the £330bn loan policy he has announced, at least £50bn worth of economic stimulus has been announced.Many other G20 countries have undertaken their own versions of what I call 'People’s QE', many of them bigger packages - the US appears to be contemplating a stimulus as much as $2 trillion.But, for the sake of illustration, if the UK package were the price for three months social distancing and this was repeated across the G20, then the total cost for all G20 countries - adjusted for relative size - would be in the vicinity of $1trillion.If this isn’t accompanied by steps involving the best therapeutics and diagnostics, and we have to keep everyone isolated for one year, it would become at least $4trillion.This may be 'back of the envelope' calculations which ignores the almost inevitable challenges for social cohesion in so many nations. But the G20 must spend something around $10bn immediately to put in absolute best standards all over the world, and another $10 bn to kickstart the market for new antibiotics.This is a version of an article that first appeared in Project Syndicate. Full Article
me Let's Emerge From COVID-19 with Stronger Health Systems By feedproxy.google.com Published On :: Thu, 26 Mar 2020 09:33:28 +0000 26 March 2020 Robert Yates Director, Global Health Programme; Executive Director, Centre for Universal Health @yates_rob Heads of state should grasp the opportunity to become universal health heroes to strengthen global health security 2020-03-26-Health-Protest A "Big Insurance: Sick of It" rally in New York City. Photo by Mario Tama/Getty Images. As the COVID-19 pandemic presents the greatest threat to human health in over a century, people turn to their states to resolve the crisis and protect their health, their livelihoods and their future well-being.How leaders perform and respond to the pandemic is likely to define their premiership - and this therefore presents a tremendous opportunity to write themselves into the history books as a great leader, rescuing their people from a crisis. Just as Winston Churchill did in World War Two.Following Churchill’s advice to “never let a good crisis go to waste”, if leaders take decisive action now, they may emerge from the COVID-19 crisis as a national hero. What leaders must do quickly is to mitigate the crisis in a way which has a demonstrable impact on people’s lives.Given the massive shock caused by the pandemic to economies across the world, it is not surprising that heads of state and treasury ministers have implemented enormous economic stimulus packages to protect businesses and jobs – this was to be expected and has been welcome.National heroes can be madeBut, in essence, this remains primarily a health crisis. And one obvious area for leaders to act rapidly is strengthening their nation’s health system to stop the spread of the virus and successfully treat those who have fallen sick. It is perhaps here that leaders have the most to gain - or lose - and where national heroes can be made.This is particularly the case in countries with weak and inequitable health systems, where the poor and vulnerable often fail to access the services they need. One major practical action that leaders can implement immediately is to launch truly universal, publicly-financed health reforms to cover their entire population – not only for COVID-19 services but for all services.This would cost around 1-2% GDP in the short-term but is perfectly affordable in the current economic climate, given some of the massive fiscal stimuluses already being planned (for example, the UK is spending 15% GDP to tackle COVID-19).Within one to two years, this financing would enable governments to implement radical supply side reforms including scaling up health workforces, increasing the supply of essential medicines, diagnostics and vaccines and building new infrastructure. It would also enable them to remove health service user fees which currently exclude hundreds of millions of people worldwide from essential healthcare. Worldwide these policies have proven to be effective, efficient, equitable and extremely popular.And there is plenty of precedent for such a move. Universal health reform is exactly what political leaders did in the UK, France and Japan as post-conflict states emerging from World War Two. It is also the policy President Kagame launched in the aftermath of the genocide in Rwanda, as did Prime Minister Thaksin in Thailand after the Asian Financial Crisis in 2002, and the Chinese leadership did following the SARS crisis, also in 2003.In China’s case, reform involved re-socialising the health financing system using around 2% GDP in tax financing to increase health insurance coverage from a low level of one-third right up to 96% of the population.All these universal health coverage (UHC) reforms delivered massive health and economic benefits to the people - just what is needed now to tackle COVID-19 - and tremendous political benefits to the leaders that implemented them.When considering the current COVID-19 crisis, this strategy would be particularly relevant for countries underperforming on health coverage and whose health systems are more likely to be overwhelmed if flooded with a surge of patients, such as India, Pakistan, Bangladesh, Myanmar, Indonesia and most of sub-Saharan Africa, where many governments spend less than 1% of their GDP on health and most people have to buy services over the counter.But also the two OECD countries without a universal health system – the United States and Ireland – are seeing the threat of COVID-19 already fuelling the debate about the need to create national, publicly-financed health system. And the presidents of South Africa, Kenya and Indonesia have already committed their governments to eventually reach full population coverage anyway, and so may use this crisis to accelerate their own universal reforms. Although difficult to predict which leaders are likely to grasp the opportunity, if some of these countries now fast-track nationwide UHC, at least something good will be coming from the crisis, something which will benefit their people forever. And ensuring everyone accesses the services they need, including public health and preventive services, also provides the best protection against any future outbreaks becoming epidemics.Every night large audiences are tuning in to press briefings fronted by their heads of state hungry for the latest update on the crisis and to get reassurance that their government’s strategy will bring the salvation they desperately need. To truly improve health security for people across the world, becoming UHC heroes could be the best strategic decision political leaders ever make. Full Article
me Emerging Lessons From COVID-19 By feedproxy.google.com Published On :: Thu, 02 Apr 2020 14:49:54 +0000 2 April 2020 Jim O'Neill Chair, Chatham House Exploring what lessons can be learned from the crisis to improve society and the functioning of our economic model going forward. 2020-04-02-COVID-Italy A man with a protective mask by the Coliseum in Rome during the height of Italy's COVID-19 epidemic. Photo by ALBERTO PIZZOLI/AFP via Getty Images. As tentative evidence emerges that Italy and Spain may have reached - or are close to - the peak of the curve, this could demonstrate that not only can Asian countries get to grips with COVID-19, but so can western democracies. And, if so, this offers a path for the rest of us.The last few weeks does demonstrate there is a role for governments to intervene in society, whether it be health, finance or any walk of life, as they have had to implement social distancing. Some have been forced, and the interventions are almost definitely only temporary, but perhaps some others may be less so.Governments of all kinds now realise there is a connection between our health system quality and our economic capability. On an index of global economic sustainability that I presided over creating when I was at Goldman Sachs, the top ten best performing countries on growth environment scores includes eight of the best performing ten countries - so far- in handling the crisis in terms of deaths relative to their population.Health system qualityThe top three on the index (last calculated in 2014) were Singapore, Hong Kong and South Korea, all of which are exemplary to the rest of us on how to deal with this mess. This suggests that once we are through this crisis, a number of larger populated countries - and their international advisors such as the IMF - might treat the quality of countries' health systems just as importantly as many of the other more standard indicators in assessing ability to deal with shocks.Policymakers have also been given a rather stark warning about other looming health disasters, especially antimicrobial resistance, of which antibiotic resistance lies at the heart. An independent review I chaired recommended 29 interventions, requiring $42 bn worth of investment, essentially peanuts compared to the costs of no solution, and the current economic collapse from COVID-19. It would seem highly likely to me that policymakers are going to treat this more seriously now.As a clear consequence of the - hopefully, temporary - global economic collapse, our environment suddenly seems to be cleaner and fresher and, in this regard, we have bought some time in the battle against climate change. Surely governments are going to be able to have a bigger influence on fossil fuel extractors and intense users as we emerge from this crisis?For any industries requiring government support, the government can make it clear this is dependent on certain criteria. And surely the days of excessive use of share buy backs and extreme maximisation of profit at the expense of other goals, are over?It seems to me an era of 'optimisation' of a number of business goals is likely to be the mantra, including profits but other things too such as national equality especially as it relates to income. Here in the UK, the government has offered its strongest fiscal support to the lower end of the income earning range group and, in a single swoop, has presided over its most dramatic step towards narrowing income inequality for a long time.This comes on top of a period of strong initiatives to support higher levels of minimum earnings, meaning we will emerge later in 2020, into 2021, and beyond, with lower levels of income inequality.The geographic issue of rural versus urban is also key. COVID-19 has spread more easily in more tightly packed cities such as London, New York and many others. More geographically remote places, by definition, are better protected. Perhaps now there will be some more thought given by policymakers to the quality and purpose of life outside our big metropolitan areas.Lastly, will China emerge from this crisis by offering a mammoth genuine gesture to the rest of the world, and come up, with, unlike, in 2008, a fiscal stimulus to its own consumers, that is geared towards importing a lot of things from the rest of the world? Now that would be good way of bringing the world back together again.This is a version of an article originally published in The Article Full Article
me In Search of the American State By feedproxy.google.com Published On :: Mon, 06 Apr 2020 12:42:29 +0000 6 April 2020 Dr Leslie Vinjamuri Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme @londonvinjamuri Google Scholar The urgent need for US leadership to drive forward a coordinated international response to coronavirus is developing rapidly alongside snowballing demands for Washington to step up its efforts at home. 2020-04-06-US-covid-washington Exercising in front of a deserted Lincoln Memorial in Washington, DC. Photo by Win McNamee/Getty Images. As the US surgeon general warns Americans to brace for ‘our Pearl Harbor moment’, the US faces a week in which it may see the worst of the global pandemic. The absence of US leadership at the global level has enabled the Security Council’s inaction. And at the G7, President Trump actively obstructed efforts to agree a joint statement.US efforts to increase its support of international aid to the tune of $274million are minimal, not least in light of a 50% reduction in its support for the World Health Organization (WHO) and radically diminished support for other global health programmes as well. International coordination is essential to mitigate unregulated competition for critical medical supplies, manage border closures, and guarantee international economic stability.True, it won’t be possible to control the epidemic at home if the global effort to defeat the pandemic fails. But the absence of leadership from Washington at home is palpable. And what happens at home sets a natural limit on America’s internationalism.Both solution and problemIn response to the coronavirus crisis, the US state is proving to be a solution - and a problem. The dramatic response to the economic crisis is evident with the $2.3trillion stimulus package signed into law by President Trump boldly supported by both Democrats and Republicans in the most significant piece of bipartisan legislation passed in decades.America’s political economy is unrecognisable, moving left and looking increasingly more European each week as Congress and the executive branch agree a series of stimulus packages designed to protect citizens and businesses. Some elements of this legislation were more familiar to Americans, notably $200bn in corporate tax breaks.But Congress also agreed unemployment insurance, and cheques - one in April, one in May – to be sent directly to those Americans most directly hit by the economic impact of COVID-19. In effect, this is adopting a temporary universal basic income.The stimulus plan also dedicated $367bn to keep small businesses afloat for as long as the economy is shuttered. Already the government is negotiating a fourth stimulus package, but the paradox is that without rigorous steps to halt the health crisis, no level of state intervention designed to solve the economic response will be sufficient.The scale of the state’s economic intervention is unprecedented, but it stands in stark contrast to Washington’s failure to coordinate a national response to America’s health crisis. An unregulated market for personal protective equipment and ventilators is driving up competition between cities, states, and even the federal government.In some cases, cities and states are reaching out directly beyond national borders to international organisations, foreign firms and even America’s geopolitical competitors as they search for suppliers. In late March, the city of New York secured a commitment from the United Nations to donate 250,000 protective face masks.Now Governor Cuomo has announced New York has secured a shipment of 140 ventilators from the state of Oregon, and 1,000 ventilators from China. The Patriots even sent their team plane to China to pick up medical supplies for the state of Massachusetts. And following a phone call between President Putin and President Trump, Russia sent a plane with masks and medical equipment to JFK airport in New York.Networks of Chinese-Americans in the United States are rapidly mobilising their networks to access supplies and send them to doctors and nurses in need. And innovative and decisive action by governors, corporates, universities and mayors drove America’s early response to coronavirus.This was critical to slowing the spread of COVID-19 by implementing policies that rapidly drove social distancing. But the limits of decentralized and uncoordinated action are now coming into sharp focus. President Trump has so far refused to require stay-at-home orders across all states, leaving this authority to individual governors. Unregulated competition has driven up prices with the consequence that critical supplies are going to the highest bidder, not those most in need.Governor Cuomo’s call for a nationwide buying consortium has so far gone unheeded and, although the Federal Emergency Management Agency has attempted to deliver supplies to states most in need, the Strategic National Stockpile is depleting fast. Without critical action, the federal government risks hindering the ability of cities and states to get the supplies they need.But President Trump is reluctant to fully deploy his powers under the Defense Production Act (DPA). In March, he did invoke the DPA to require certain domestic manufacturers to produce ventilators. But calls for it to be used to require manufacturers to produce PPE (personal protective equipment), control costs, and manage allocations has so far gone unheeded by a president generally opposed to state interventions for managing the economy.It is true that federalism and a deep belief in competition are critical to the fabric of US history and politics, and innovations made possible by market values of entrepreneurism and competition cannot be underestimated. In the search for a vaccine, this could still prove to be key.But with current estimates that more Americans will die from coronavirus than were killed in the Korean and Vietnam wars combined, it is clear now is the time to reimagine and reinvent the role of the American state.In the absence of a coordinated effort driven by the White House, governors are working together to identify the areas of greatest need. Whether this will lead to a recasting of the American state and greater demand for a deeper and more permanent social safety net is a key question in the months ahead.In the short-term the need for coordinated state action at the national level is self-evident. US leadership globally, to manage the health crisis and its economic impacts, is also vital. But this is unlikely to be forthcoming until America gets its own house in order. Full Article
me Webinar: Investing in Mental Health Policy By feedproxy.google.com Published On :: Tue, 07 Apr 2020 22:00:01 +0000 Members Event 17 April 2020 - 1:00pm to 2:00pm Online Event participants Undersecretary Myrna C Cabotaje, Public Health Services Team, Department of Health, PhilippinesAlan Jope, CEO, UnileverJosephine Karwah, Mental Health AdvocateDr Dévora Kestel, Director, Mental Health and Substance Use Department, World Health OrganizationChair: Robert Yates, Director, Global Health Programme and Executive Director, Centre for Universal Health, Chatham House Panellists discuss the significance of investing in mental health and the return on the individual, the economy and society. Although the economic and societal benefits of investing in health are increasingly recognized, less than two per cent of national health budgets globally are spent on mental health, despite the enormous impact it has on citizens and countries around the world. With the global health emergency of COVID-19 accelerating conversations around mental wellness and productivity, governments around the world are under increasing pressure to respond to the immediate challenges of ensuring both physical and mental health. Given that mental illness typically rises in times of economic recession and health crises, how are individuals, businesses and societies thinking about this issue? How can governments ensure mental health is integrated in global health coverage? And what role does technology play in mental health provision?This event was run in partnership with United for Global Mental Health, within the framework of the Speak Your Mind (SYM) nationally led and globally united campaign that calls on leaders to provide quality mental health for all. UnitedGMH aims to unite global efforts on mental health and provides advocacy, campaigning and financing support to global institutions, businesses, communities and individual change-makers seeking greater action on global mental health. Members Events Team Email Full Article
me Coronavirus: Public Health Emergency or Pandemic – Does Timing Matter? By feedproxy.google.com Published On :: Fri, 01 May 2020 14:48:43 +0000 1 May 2020 Dr Charles Clift Senior Consulting Fellow, Global Health Programme @CliftWorks The World Health Organization (WHO) has been criticized for delaying its announcements of a public health emergency and a pandemic for COVID-19. But could earlier action have influenced the course of events? 2020-05-01-Tedros-WHO-COVID WHO director-general Dr Tedros Adhanom Ghebreyesus at the COVID-19 press briefing on March 11, 2020, the day the coronavirus outbreak was classed as a pandemic. Photo by FABRICE COFFRINI/AFP via Getty Images. The World Health Organization (WHO) declared the spread of COVID-19 to be a Public Health Emergency of International Concern (PHEIC) on January 30 this year and then characterized it as a pandemic on March 11.Declaring a PHEIC is the highest level of alert that WHO is obliged to declare, and is meant to send a powerful signal to countries of the need for urgent action to combat the spread of the disease, mobilize resources to help low- and middle-income countries in this effort and fund research and development on needed treatments, vaccines and diagnostics. It also obligates countries to share information with WHO.Once the PHEIC was declared, the virus continued to spread globally, and WHO began to be asked why it had not yet declared the disease a pandemic. But there is no widely accepted definition of a pandemic, generally it is just considered an epidemic which affects many countries globally.Potentially more deadlyThe term has hitherto been applied almost exclusively to new forms of flu, such as H1N1 in 2009 or Spanish flu in 1918, where the lack of population immunity and absence of a vaccine or effective treatments makes the outbreak potentially much more deadly than seasonal flu (which, although global, is not considered a pandemic).For COVID-19, WHO seemed reluctant to declare a pandemic despite the evidence of global spread. Partly this was because of its influenza origins — WHO’s emergency programme executive director said on March 9 that ‘if this was influenza, we would have called a pandemic ages ago’.He also expressed concern that the word traditionally meant moving — once there was widespread transmission — from trying to contain the disease by testing, isolating the sick and tracing and quarantining their contacts, to a mitigation approach, implying ‘the disease will spread uncontrolled’.WHO’s worry was that the world’s reaction to the word pandemic might be there was now nothing to be done to stop its spread, and so countries would effectively give up trying. WHO wanted to send the message that, unlike flu, it could still be pushed back and the spread slowed down.In announcing the pandemic two days later, WHO’s director-general Dr Tedros Adhanom Ghebreyesus reemphasised this point: ‘We cannot say this loudly enough, or clearly enough, or often enough: all countries can still change the course of this pandemic’ and that WHO was deeply concerned ‘by the alarming levels of inaction’.The evidence suggests that the correct message did in fact get through. On March 13, US president Donald Trump declared a national emergency, referring in passing to WHO’s announcement. On March 12, the UK launched its own strategy to combat the disease. And in the week following WHO’s announcements, at least 16 other countries announced lockdowns of varying rigour including Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Netherlands, Norway, Poland, Portugal, Serbia, Spain and Switzerland. Italy and Greece had both already instituted lockdowns prior to the WHO pandemic announcement.It is not possible to say for sure that WHO’s announcement precipitated these measures because, by then, the evidence of the rapid spread was all around for governments to see. It may be that Italy’s dramatic nationwide lockdown on March 9 reverberated around European capitals and elsewhere.But it is difficult to believe the announcement did not have an effect in stimulating government actions, as was intended by Dr Tedros. Considering the speed with which the virus was spreading from late February, might an earlier pandemic announcement by WHO have stimulated earlier aggressive actions by governments?Declaring a global health emergency — when appropriate — is a key part of WHO’s role in administering the International Health Regulations (IHR). Significantly, negotiations on revisions to the IHR, which had been ongoing in a desultory fashion in WHO since 1995, were accelerated by the experience of the first serious coronavirus outbreak — SARS — in 2002-2003, leading to their final agreement in 2005.Under the IHR, WHO’s director-general decides whether to declare an emergency based on a set of criteria and on the advice of an emergency committee. IHR defines an emergency as an ‘extraordinary event that constitutes a public health risk through the international spread of disease and potentially requires a coordinated international response’.In the case of COVID-19, the committee first met on January 22-23 but were unable to reach consensus on a declaration. Following the director-general’s trip to meet President Xi Jinping in Beijing, the committee reconvened on January 30 and this time advised declaring a PHEIC.But admittedly, public recognition of what a PHEIC means is extremely low. Only six have ever been declared, with the first being the H1N1 flu outbreak which fizzled out quickly, despite possibly causing 280,000 deaths globally. During the H1N1 outbreak, WHO declared a PHEIC in April 2009 and then a pandemic in June, only to rescind both in August as the outbreak was judged to have transitioned to behave like a seasonal flu.WHO was criticized afterwards for prematurely declaring a PHEIC and overreacting. This then may have impacted the delay in declaring the Ebola outbreak in West Africa as a PHEIC in 2014, long after it became a major crisis. WHO’s former legal counsel has suggested the PHEIC — and other aspects of the IHR framework — may not be effective in stimulating appropriate actions by governments and needs to be reconsidered.When the time is right to evaluate lessons about the response, it might be appropriate to consider the relative effectiveness of the PHEIC and pandemic announcements and their optimal timing in stimulating appropriate action by governments. The effectiveness of lockdowns in reducing the overall death toll also needs investigation. Full Article
me The transcriptional regulator MEIS2 sets up the ground state for palatal osteogenesis in mice [Gene Regulation] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Haploinsufficiency of Meis homeobox 2 (MEIS2), encoding a transcriptional regulator, is associated with human cleft palate, and Meis2 inactivation leads to abnormal palate development in mice, implicating MEIS2 functions in palate development. However, its functional mechanisms remain unknown. Here we observed widespread MEIS2 expression in the developing palate in mice. Wnt1Cre-mediated Meis2 inactivation in cranial neural crest cells led to a secondary palate cleft. Importantly, about half of the Wnt1Cre;Meis2f/f mice exhibited a submucous cleft, providing a model for studying palatal bone formation and patterning. Consistent with complete absence of palatal bones, the results from integrative analyses of MEIS2 by ChIP sequencing, RNA-Seq, and an assay for transposase-accessible chromatin sequencing identified key osteogenic genes regulated directly by MEIS2, indicating that it plays a fundamental role in palatal osteogenesis. De novo motif analysis uncovered that the MEIS2-bound regions are highly enriched in binding motifs for several key osteogenic transcription factors, particularly short stature homeobox 2 (SHOX2). Comparative ChIP sequencing analyses revealed genome-wide co-occupancy of MEIS2 and SHOX2 in addition to their colocalization in the developing palate and physical interaction, suggesting that SHOX2 and MEIS2 functionally interact. However, although SHOX2 was required for proper palatal bone formation and was a direct downstream target of MEIS2, Shox2 overexpression failed to rescue the palatal bone defects in a Meis2-mutant background. These results, together with the fact that Meis2 expression is associated with high osteogenic potential and required for chromatin accessibility of osteogenic genes, support a vital function of MEIS2 in setting up a ground state for palatal osteogenesis. Full Article
me The mRNA levels of heat shock factor 1 are regulated by thermogenic signals via the cAMP-dependent transcription factor ATF3 [Metabolism] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues. Full Article
me The histone H4 basic patch regulates SAGA-mediated H2B deubiquitination and histone acetylation [DNA and Chromosomes] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications. Full Article
me On the measure of maximal entropy for finite horizon Sinai Billiard maps By www.ams.org Published On :: Tue, 10 Mar 2020 10:59 EDT Viviane Baladi and Mark F. Demers J. Amer. Math. Soc. 33 (2020), 381-449. Abstract, references and article information Full Article
me Cohomologie ????-adique de la tour de Drinfeld: le cas de la dimension 1 By www.ams.org Published On :: Tue, 10 Mar 2020 10:59 EDT Pierre Colmez, Gabriel Dospinescu and Wiesława Nizioł J. Amer. Math. Soc. 33 (2019), 311-362. Abstract, references and article information Full Article
me The Human Plasma Proteome: A Nonredundant List Developed by Combination of Four Separate Sources By feedproxy.google.com Published On :: 2004-04-01 N. Leigh AndersonApr 1, 2004; 3:311-326Research Full Article
me Proteomics of the Chloroplast Envelope Membranes from Arabidopsis thaliana By feedproxy.google.com Published On :: 2003-05-01 Myriam FerroMay 1, 2003; 2:325-345Research Full Article
me Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation By feedproxy.google.com Published On :: 2015-03-01 Michal Bassani-SternbergMar 1, 2015; 14:658-673Research Full Article
me Extending the Limits of Quantitative Proteome Profiling with Data-Independent Acquisition and Application to Acetaminophen-Treated Three-Dimensional Liver Microtissues By feedproxy.google.com Published On :: 2015-05-01 Roland BrudererMay 1, 2015; 14:1400-1410Research Full Article
me Phosphoproteome Analysis of E. coli Reveals Evolutionary Conservation of Bacterial Ser/Thr/Tyr Phosphorylation By feedproxy.google.com Published On :: 2008-02-01 Boris MacekFeb 1, 2008; 7:299-307Research Full Article
me High Resolution Clear Native Electrophoresis for In-gel Functional Assays and Fluorescence Studies of Membrane Protein Complexes By feedproxy.google.com Published On :: 2007-07-01 Ilka WittigJul 1, 2007; 6:1215-1225Research Full Article
me In Vivo Identification of Human Small Ubiquitin-like Modifier Polymerization Sites by High Accuracy Mass Spectrometry and an in Vitro to in Vivo Strategy By feedproxy.google.com Published On :: 2008-01-01 Ivan MaticJan 1, 2008; 7:132-144Research Full Article
me Quantitative, Multiplexed Assays for Low Abundance Proteins in Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution By feedproxy.google.com Published On :: 2007-12-01 Hasmik KeshishianDec 1, 2007; 6:2212-2229Research Full Article
me The Proteome of the Mouse Photoreceptor Sensory Cilium Complex By feedproxy.google.com Published On :: 2007-08-01 Qin LiuAug 1, 2007; 6:1299-1317Research Full Article
me Time-resolved Mass Spectrometry of Tyrosine Phosphorylation Sites in the Epidermal Growth Factor Receptor Signaling Network Reveals Dynamic Modules By feedproxy.google.com Published On :: 2005-09-01 Yi ZhangSep 1, 2005; 4:1240-1250Research Full Article
me Complementary Profiling of Gene Expression at the Transcriptome and Proteome Levels in Saccharomyces cerevisiae By feedproxy.google.com Published On :: 2002-04-01 Timothy J. GriffinApr 1, 2002; 1:323-333Research Full Article
me Toward a Comprehensive Atlas of the Physical Interactome of Saccharomyces cerevisiae By feedproxy.google.com Published On :: 2007-03-01 Sean R. CollinsMar 1, 2007; 6:439-450Research Full Article
me A Proteome-wide, Quantitative Survey of In Vivo Ubiquitylation Sites Reveals Widespread Regulatory Roles By feedproxy.google.com Published On :: 2011-10-01 Sebastian A. WagnerOct 1, 2011; 10:M111.013284-M111.013284Research Full Article
me Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis By feedproxy.google.com Published On :: 2012-06-01 Ludovic C. GilletJun 1, 2012; 11:O111.016717-O111.016717Research Full Article
me A Multidimensional Chromatography Technology for In-depth Phosphoproteome Analysis By feedproxy.google.com Published On :: 2008-07-01 Claudio P. AlbuquerqueJul 1, 2008; 7:1389-1396Research Full Article
me Comparison of Label-free Methods for Quantifying Human Proteins by Shotgun Proteomics By feedproxy.google.com Published On :: 2005-10-01 William M. OldOct 1, 2005; 4:1487-1502Research Full Article
me Quantitative Mass Spectrometric Multiple Reaction Monitoring Assays for Major Plasma Proteins By feedproxy.google.com Published On :: 2006-04-01 Leigh AndersonApr 1, 2006; 5:573-588Research Full Article
me Highly Selective Enrichment of Phosphorylated Peptides from Peptide Mixtures Using Titanium Dioxide Microcolumns By feedproxy.google.com Published On :: 2005-07-01 Martin R. LarsenJul 1, 2005; 4:873-886Technology Full Article
me The Human Plasma Proteome: History, Character, and Diagnostic Prospects By feedproxy.google.com Published On :: 2002-11-01 N. Leigh AndersonNov 1, 2002; 1:845-867Reviews/Perspectives Full Article
me Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics By feedproxy.google.com Published On :: 2014-02-01 Linn FagerbergFeb 1, 2014; 13:397-406Research Full Article
me Parts per Million Mass Accuracy on an Orbitrap Mass Spectrometer via Lock Mass Injection into a C-trap By feedproxy.google.com Published On :: 2005-12-01 Jesper V. OlsenDec 1, 2005; 4:2010-2021Technology Full Article
me Accurate Proteome-wide Label-free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ By feedproxy.google.com Published On :: 2014-09-01 Jürgen CoxSep 1, 2014; 13:2513-2526Technological Innovation and Resources Full Article
me The hibernating 100S complex is a target of ribosome-recycling factor and elongation factor G in Staphylococcus aureus [Protein Synthesis and Degradation] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The formation of translationally inactive 70S dimers (called 100S ribosomes) by hibernation-promoting factor is a widespread survival strategy among bacteria. Ribosome dimerization is thought to be reversible, with the dissociation of the 100S complexes enabling ribosome recycling for participation in new rounds of translation. The precise pathway of 100S ribosome recycling has been unclear. We previously found that the heat-shock GTPase HflX in the human pathogen Staphylococcus aureus is a minor disassembly factor. Cells lacking hflX do not accumulate 100S ribosomes unless they are subjected to heat exposure, suggesting the existence of an alternative pathway during nonstressed conditions. Here, we provide biochemical and genetic evidence that two essential translation factors, ribosome-recycling factor (RRF) and GTPase elongation factor G (EF-G), synergistically split 100S ribosomes in a GTP-dependent but tRNA translocation-independent manner. We found that although HflX and the RRF/EF-G pair are functionally interchangeable, HflX is expressed at low levels and is dispensable under normal growth conditions. The bacterial RRF/EF-G pair was previously known to target only the post-termination 70S complexes; our results reveal a new role in the reversal of ribosome hibernation that is intimately linked to bacterial pathogenesis, persister formation, stress responses, and ribosome integrity. Full Article
me The cytochrome P450 enzyme CYP24A1 increases proliferation of mutant KRAS-dependent lung adenocarcinoma independent of its catalytic activity [Cell Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high. Full Article
me {gamma}-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Hypersecretion of glucagon from pancreatic α-cells strongly contributes to diabetic hyperglycemia. Moreover, failure of α-cells to increase glucagon secretion in response to falling blood glucose concentrations compromises the defense against hypoglycemia, a common complication in diabetes therapy. However, the mechanisms underlying glucose regulation of glucagon secretion are poorly understood and likely involve both α-cell–intrinsic and intraislet paracrine signaling. Among paracrine factors, glucose-stimulated release of the GABA metabolite γ-hydroxybutyric acid (GHB) from pancreatic β-cells might mediate glucose suppression of glucagon release via GHB receptors on α-cells. However, the direct effects of GHB on α-cell signaling and glucagon release have not been investigated. Here, we found that GHB (4–10 μm) lacked effects on the cytoplasmic concentrations of the secretion-regulating messengers Ca2+ and cAMP in mouse α-cells. Glucagon secretion from perifused mouse islets was also unaffected by GHB at both 1 and 7 mm glucose. The GHB receptor agonist 3-chloropropanoic acid and the antagonist NCS-382 had no effects on glucagon secretion and did not affect stimulation of secretion induced by a drop in glucose from 7 to 1 mm. Inhibition of endogenous GHB formation with the GABA transaminase inhibitor vigabatrin also failed to influence glucagon secretion at 1 mm glucose and did not prevent the suppressive effect of 7 mm glucose. In human islets, GHB tended to stimulate glucagon secretion at 1 mm glucose, an effect mimicked by 3-chloropropanoic acid. We conclude that GHB does not mediate the inhibitory effect of glucose on glucagon secretion. Full Article
me Heterotrimeric Gq proteins as therapeutic targets? [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Heterotrimeric G proteins are the core upstream elements that transduce and amplify the cellular signals from G protein–coupled receptors (GPCRs) to intracellular effectors. GPCRs are the largest family of membrane proteins encoded in the human genome and are the targets of about one-third of prescription medicines. However, to date, no single therapeutic agent exerts its effects via perturbing heterotrimeric G protein function, despite a plethora of evidence linking G protein malfunction to human disease. Several recent studies have brought to light that the Gq family–specific inhibitor FR900359 (FR) is unexpectedly efficacious in silencing the signaling of Gq oncoproteins, mutant Gq variants that mostly exist in the active state. These data not only raise the hope that researchers working in drug discovery may be able to potentially strike Gq oncoproteins from the list of undruggable targets, but also raise questions as to how FR achieves its therapeutic effect. Here, we place emphasis on these recent studies and explain why they expand our pharmacological armamentarium for targeting Gq protein oncogenes as well as broaden our mechanistic understanding of Gq protein oncogene function. We also highlight how this novel insight impacts the significance and utility of using G(q) proteins as targets in drug discovery efforts. Full Article
me ABC transporters control ATP release through cholesterol-dependent volume-regulated anion channel activity [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling. Full Article
me Noncatalytic Bruton's tyrosine kinase activates PLC{gamma}2 variants mediating ibrutinib resistance in human chronic lymphocytic leukemia cells [Membrane Biology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs. Full Article
me Reduction of protein phosphatase 2A (PP2A) complexity reveals cellular functions and dephosphorylation motifs of the PP2A/B'{delta} holoenzyme [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Protein phosphatase 2A (PP2A) is a large enzyme family responsible for most cellular Ser/Thr dephosphorylation events. PP2A substrate specificity, localization, and regulation by second messengers rely on more than a dozen regulatory subunits (including B/R2, B'/R5, and B″/R3), which form the PP2A heterotrimeric holoenzyme by associating with a dimer comprising scaffolding (A) and catalytic (C) subunits. Because of partial redundancy and high endogenous expression of PP2A holoenzymes, traditional approaches of overexpressing, knocking down, or knocking out PP2A regulatory subunits have yielded only limited insights into their biological roles and substrates. To this end, here we sought to reduce the complexity of cellular PP2A holoenzymes. We used tetracycline-inducible expression of pairs of scaffolding and regulatory subunits with complementary charge-reversal substitutions in their interaction interfaces. For each of the three regulatory subunit families, we engineered A/B charge–swap variants that could bind to one another, but not to endogenous A and B subunits. Because endogenous Aα was targeted by a co-induced shRNA, endogenous B subunits were rapidly degraded, resulting in expression of predominantly a single PP2A heterotrimer composed of the A/B charge–swap pair and the endogenous catalytic subunit. Using B'δ/PPP2R5D, we show that PP2A complexity reduction, but not PP2A overexpression, reveals a role of this holoenzyme in suppression of extracellular signal–regulated kinase signaling and protein kinase A substrate dephosphorylation. When combined with global phosphoproteomics, the PP2A/B'δ reduction approach identified consensus dephosphorylation motifs in its substrates and suggested that residues surrounding the phosphorylation site play roles in PP2A substrate specificity. Full Article
me G{alpha}q splice variants mediate phototransduction, rhodopsin synthesis, and retinal integrity in Drosophila [Signal Transduction] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Heterotrimeric G proteins mediate a variety of signaling processes by coupling G protein–coupled receptors to intracellular effector molecules. In Drosophila, the Gαq gene encodes several Gαq splice variants, with the Gαq1 isoform protein playing a major role in fly phototransduction. However, Gαq1 null mutant flies still exhibit a residual light response, indicating that other Gαq splice variants or additional Gq α subunits are involved in phototransduction. Here, we isolated a mutant fly with no detectable light responses, decreased rhodopsin (Rh) levels, and rapid retinal degeneration. Using electrophysiological and genetic studies, biochemical assays, immunoblotting, real-time RT-PCR, and EM analysis, we found that mutations in the Gαq gene disrupt light responses and demonstrate that the Gαq3 isoform protein is responsible for the residual light response in Gαq1 null mutants. Moreover, we report that Gαq3 mediates rhodopsin synthesis. Depletion of all Gαq splice variants led to rapid light-dependent retinal degeneration, due to the formation stable Rh1-arrestin 2 (Arr2) complexes. Our findings clarify essential roles of several different Gαq splice variants in phototransduction and retinal integrity in Drosophila and reveal that Gαq3 functions in rhodopsin synthesis. Full Article