s:

Mechanisms of Pancreatic {beta}-Cell Death in Type 1 and Type 2 Diabetes: Many Differences, Few Similarities

Miriam Cnop
Dec 1, 2005; 54:S97-S107
Section III: Inflammation and beta-Cell Death




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Low-Grade Systemic Inflammation and the Development of Type 2 Diabetes: The Atherosclerosis Risk in Communities Study

Bruce B. Duncan
Jul 1, 2003; 52:1799-1805
Pathophysiology




s:

The Pathobiology of Diabetic Complications: A Unifying Mechanism

Michael Brownlee
Jun 1, 2005; 54:1615-1625
Banting Lecture 2004




s:

Latent Autoimmune Diabetes in Adults: Definition, Prevalence, {beta}-Cell Function, and Treatment

Gunnar Stenström
Dec 1, 2005; 54:S68-S72
Section II: Type 1-Related Forms of Diabetes




s:

Sources: Giants add Parra to outfield mix

As they continue to await a resolution to the Bryce Harper sweepstakes, the Giants augmented their outfield depth by signing veteran Gerardo Parra to a Minor League deal Tuesday, sources confirmed to MLB.com's Jon Paul Morosi and Mark Feinsand.




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Melding the best of two worlds: Cecil Pickett's work on cellular oxidative stress and in drug discovery and development [Molecular Bases of Disease]

Many chemicals and cellular processes cause oxidative stress that can damage lipids, proteins, or DNA (1). To quickly sense and respond to this ubiquitous threat, organisms have evolved enzymes that neutralize harmful oxidants such as reactive oxygen species and electrophilic compounds (including xenobiotics and their breakdown products) in cells.These antioxidant enzymes include GSH S-transferase (GST),2 NADPH:quinone oxidoreductase 1, thioredoxin, hemeoxygenase-1, and others (2, 3). Many of these proteins are commonly expressed in cells exposed to oxidative stress.The antioxidant response element (ARE) is a major regulatory component of this cellular stress response. The ARE is a conserved, 11-nucleotide-long DNA motif present in the 5'-flanking regions of many genes encoding antioxidant proteins. The laboratory of Cecil Pickett (Fig. 1) at the Merck Frosst Centre for Therapeutic Research in Quebec discovered ARE, a finding reported in the early 1990s in two JBC papers recognized as Classics here (4, 5).jbc;295/12/3929/F1F1F1Figure 1.Cecil Pickett (pictured) and colleagues first described the ARE motif, present in the 5' regions of many genes whose expression is up-regulated by oxidative stress and xenobiotics. Photo courtesy of Cecil Pickett.ARE's discovery was spurred in large part by Pickett's career choice. After completing a PhD in biology and a 2-year postdoc at UCLA in the mid-1970s, he began to work in the pharmaceutical industry.Recruited to Merck in 1978 by its then head of research and development (and later CEO), Roy Vagelos, “I became interested in how drug-metabolizing enzymes were induced by various xenobiotics,” Pickett says.According to Pickett, Vagelos encouraged researchers at the company...




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Tackling Cyber Disinformation in Elections: Applying International Human Rights Law

Research Event

6 November 2019 - 5:30pm to 7:00pm

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

Event participants

Susie Alegre, Barrister and Associate Tenant, Doughty Street Chambers
Evelyn Aswad, Professor of Law and the Herman G. Kaiser Chair in International Law, University of Oklahoma
Barbora Bukovská, Senior Director for Law and Policy, Article 19
Kate Jones, Director, Diplomatic Studies Programme, University of Oxford
Chair: Harriet Moynihan, Associate Fellow, International Law Programme, Chatham House

Cyber operations are increasingly used by political parties, their supporters and foreign states to influence electorates – from algorithms promoting specific messages to micro-targeting based on personal data and the creation of filter bubbles.
 
The risks of digital tools spreading disinformation and polarizing debate, as opposed to deepening democratic engagement, have been highlighted by concerns over cyber interference in the UK’s Brexit referendum, the 2016 US presidential elections and in Ukraine. 
 
While some governments are adopting legislation in an attempt to address some of these issues, for example Germany’s ‘NetzDG’ law and France’s ‘Law against the manipulation of information’, other countries have proposed an independent regulator as in the case of the UK’s Online Harms white paper. Meanwhile, the digital platforms, as the curators of content, are under increasing pressure to take their own measures to address data mining and manipulation in the context of elections. 

How do international human rights standards, for example on freedom of thought, expression and privacy, guide the use of digital technology in the electoral context? What practical steps can governments and technology actors take to ensure policies, laws and practices are in line with these fundamental standards? And with a general election looming in the UK, will these steps come soon enough?
 
This event brings together a wide range of stakeholders including civil society, the tech sector, legal experts and government, coincides with the publication of a Chatham House research paper on disinformation, elections and the human rights framework

Jacqueline Rowe

Programme Assistant, International Law Programme
020 7389 3287




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Human Rights Priorities: An Agenda for Equality and Social Justice

Members Event

19 November 2019 - 6:00pm to 7:00pm

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

Event participants

Michelle Bachelet, United Nations High Commissioner for Human Rights

Chair: Ruma Mandal, Head, International Law Programme, Chatham House

Following just over one year in office, UN High Commissioner for Human Rights, Michelle Bachelet, outlines her ongoing priorities at a tumultuous time for fundamental rights protections worldwide.

She discusses the rights implications of climate change, gender inequality including the advancement of sexual and reproductive rights, the protection of vulnerable groups and the need to work closely with states, civil society and business to protect and advance human rights.

Department/project

Members Events Team




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The Application of International Law to State Cyberattacks: Sovereignty and Non-Intervention

2 December 2019

Hostile cyber operations by one state against another state are increasingly common. This paper analyzes the application of the sovereignty and non-intervention principles in relation to states’ cyber operations in another state below the threshold of the use of force. 

Harriet Moynihan

Senior Research Fellow, International Law Programme

2019-11-29-Intl-Law-Cyberattacks.jpg

A computer hacked by a virus known as Petya. The Petya ransomware cyberattack hit computers of Russian and Ukrainian companies on 27 June 2017. Photo: Getty Images.

Summary

  • The vast majority of state-to-state cyberattacks consist of persistent, low-level intrusions that take place below the threshold of use of force. International law, including the principle of non-intervention in another state’s internal affairs and the principle of sovereignty, applies to these cyber operations.
  • It is not clear whether any unauthorized cyber intrusion would violate the target state’s sovereignty, or whether there is a threshold in operation. While some would like to set limits by reference to effects of the cyber activity, at this time such limits are not reflected in customary international law. The assessment of whether sovereignty has been violated therefore has to be made on a case by case basis, if no other more specific rules of international law apply.
  • In due course, further state practice and opinio iuris may give rise to an emerging cyber-specific understanding of sovereignty, just as specific rules deriving from the sovereignty principle have crystallized in other areas of international law.
  • Before a principle of due diligence can be invoked in the cyber context, further work is needed by states to agree upon rules as to what might be expected of a state in this context.
  • The principle of non-intervention applies to a state’s cyber operations as it does to other state activities. It consists of coercive behaviour by one state that deprives the target state of its free will in relation to the exercise of its sovereign functions in order to compel an outcome in, or conduct with respect to, a matter reserved to the target state.
  • In practice, activities that contravene the non-intervention principle and activities that violates sovereignty will often overlap.
  • In order to reach agreement on how international law applies to states’ cyber operations below the level of use of force, states should put their views on record, where possible giving examples of when they consider that an obligation may be breached, as states such as the UK, Australia, France and the Netherlands have done.
  • Further discussion between states should focus on how the rules apply to practical examples of state-sponsored cyber operations. There is likely to be more commonality about specific applications of the law than there is about abstract principles.
  • The prospects of a general treaty in this area are still far off. In due course, there may be benefit in considering limited rules, for example on due diligence and a prohibition on attacking critical infrastructure, before tackling broad principles.




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Seventy Years of the Geneva Conventions: What of the Future?

24 March 2020

Seventy years after the adoption of the Geneva Conventions, there are challenges that remain to be addressed. This briefing takes three pertinent examples, and discusses possibilities for addressing them.

Emanuela-Chiara Gillard

Associate Fellow, International Law Programme

GettyImages-913468402.jpg

Rescue of the wounded in Duma city by Syrian Red Crescent paramedics, 2 February 2018. Photo: Samer Bouidani/NurPhoto/Getty

Summary

  • The 70th anniversary of the adoption of the 1949 Geneva Conventions was commemorated in 2019. But violations of the Conventions and of the 1977 Additional Protocols are widespread.
  • Contemporary conflicts have been marked by violations of some of the foundational rules of international humanitarian law (IHL) relating to the protection of the wounded and sick and of providers of medical assistance.
  • A further area of IHL that has come under strain and scrutiny are the rules regulating humanitarian relief operations and their application to sieges and blockades.
  • War has a huge impact on children, and the treatment of children in armed conflict is another area of the law that requires further attention.
  • In the current political climate, it is unlikely that new treaties will be negotiated to address emerging issues or uncertainties in the law.
  • Other measures must be explored, including the adoption of domestic measures to implement existing law; support for processes that interpret the law; and initiatives to promote compliance with the law by organized armed groups.
  • One overarching challenge is the interplay between IHL and counterterrorism measures. It can undermine the protections set out in IHL, and hinder principled humanitarian action and activities to promote compliance with the law by organized armed groups.




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Legal Provision for Crisis Preparedness: Foresight not Hindsight

21 April 2020

Dr Patricia Lewis

Research Director, Conflict, Science & Transformation; Director, International Security Programme
COVID-19 is proving to be a grave threat to humanity. But this is not a one-off, there will be future crises, and we can be better prepared to mitigate them.

2020-04-21-Nurse-COVID-Test

Examining a patient while testing for COVID-19 at the Velocity Urgent Care in Woodbridge, Virginia. Photo by Chip Somodevilla/Getty Images.

A controversial debate during COVID-19 is the state of readiness within governments and health systems for a pandemic, with lines of the debate drawn on the issues of testing provision, personal protective equipment (PPE), and the speed of decision-making.

President Macron in a speech to the nation admitted French medical workers did not have enough PPE and that mistakes had been made: ‘Were we prepared for this crisis? We have to say that no, we weren’t, but we have to admit our errors … and we will learn from this’.

In reality few governments were fully prepared. In years to come, all will ask: ‘how could we have been better prepared, what did we do wrong, and what can we learn?’. But after every crisis, governments ask these same questions.

Most countries have put in place national risk assessments and established processes and systems to monitor and stress-test crisis-preparedness. So why have some countries been seemingly better prepared?

Comparing different approaches

Some have had more time and been able to watch the spread of the disease and learn from those countries that had it first. Others have taken their own routes, and there will be much to learn from comparing these different approaches in the longer run.

Governments in Asia have been strongly influenced by the experience of the SARS epidemic in 2002-3 and - South Korea in particular - the MERS-CoV outbreak in 2015 which was the largest outside the Middle East. Several carried out preparatory work in terms of risk assessment, preparedness measures and resilience planning for a wide range of threats.

Case Study of Preparedness: South Korea

By 2007, South Korea had established the Division of Public Health Crisis Response in Korea Centers for Disease Control and Prevention (KCDC) and, in 2016, the KCDC Center for Public Health Emergency Preparedness and Response had established a round-the-clock Emergency Operations Center with rapid response teams.

KCDC is responsible for the distribution of antiviral stockpiles to 16 cities and provinces that are required by law to hold and manage antiviral stockpiles.

And, at the international level, there are frameworks for preparedness for pandemics. The International Health Regulations (IHR) - adopted at the 2005 World Health Assembly and binding on member states - require countries to report certain disease outbreaks and public health events to the World Health Organization (WHO) and ‘prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks, and which avoid unnecessary interference with international traffic and trade’.

Under IHR, governments committed to a programme of building core capacities including coordination, surveillance, response and preparedness. The UN Sendai Framework for Disaster Risk highlights disaster preparedness for effective response as one of its main purposes and has already incorporated these measures into the Sustainable Development Goals (SDGs) and other Agenda 2030 initiatives. UN Secretary-General António Guterres has said COVID-19 ‘poses a significant threat to the maintenance of international peace and security’ and that ‘a signal of unity and resolve from the Council would count for a lot at this anxious time’.

Case Study of Preparedness: United States

The National Institutes of Health (NIH) and the Center for Disease Control (CDC) established PERRC – the Preparedness for Emergency Response Research Centers - as a requirement of the 2006 Pandemic and All-Hazards Preparedness Act, which required research to ‘improve federal, state, local, and tribal public health preparedness and response systems’.

The 2006 Act has since been supplanted by the 2019 Pandemic and All-Hazards Preparedness and Advancing Innovation Act. This created the post of Assistant Secretary for Preparedness and Response (ASPR) in the Department for Health and Human Services (HHS) and authorised the development and acquisitions of medical countermeasures and a quadrennial National Health Security Strategy.

The 2019 Act also set in place a number of measures including the requirement for the US government to re-evaluate several important metrics of the Public Health Emergency Preparedness cooperative agreement and the Hospital Preparedness Program, and a requirement for a report on the states of preparedness and response in US healthcare facilities.

This pandemic looks set to continue to be a grave threat to humanity. But there will also be future pandemics – whether another type of coronavirus or a new influenza virus – and our species will be threatened again, we just don’t know when.

Other disasters too will befall us – we already see the impacts of climate change arriving on our doorsteps characterised by increased numbers and intensity of floods, hurricanes, fires, crop failure and other manifestations of a warming, increasingly turbulent atmosphere and we will continue to suffer major volcanic eruptions, earthquakes and tsunamis. All high impact, unknown probability events.

Preparedness for an unknown future is expensive and requires a great deal of effort for events that may not happen within the preparers’ lifetimes. It is hard to imagine now, but people will forget this crisis, and revert to their imagined projections of the future where crises don’t occur, and progress follows progress. But history shows us otherwise.

Preparations for future crises always fall prey to financial cuts and austerity measures in lean times unless there is a mechanism to prevent that. Cost-benefit analyses will understandably tend to prioritise the urgent over the long-term. So governments should put in place legislation – or strengthen existing legislation – now to ensure their countries are as prepared as possible for whatever crisis is coming.

Such a legal requirement would require governments to report back to parliament every year on the state of their national preparations detailing such measures as:

  • The exact levels of stocks of essential materials (including medical equipment)
  • The ability of hospitals to cope with large influx of patients
  • How many drills, exercises and simulations had been organised – and their findings
  • What was being done to implement lessons learned & improve preparedness

In addition, further actions should be taken:

  • Parliamentary committees such as the UK Joint Committee on the National Security Strategy should scrutinise the government’s readiness for the potential threats outlined in the National Risk register for Civil Emergencies in-depth on an annual basis.
  • Parliamentarians, including ministers, with responsibility for national security and resilience should participate in drills, table-top exercises and simulations to see for themselves the problems inherent with dealing with crises.
  • All governments should have a minister (or equivalent) with the sole responsibility for national crisis preparedness and resilience. The Minister would be empowered to liaise internationally and coordinate local responses such as local resilience groups.
  • There should be ring-fenced budget lines in annual budgets specifically for preparedness and resilience measures, annually reported on and assessed by parliaments as part of the due diligence process.

And at the international level:

  • The UN Security Council should establish a Crisis Preparedness Committee to bolster the ability of United Nations Member States to respond to international crisis such as pandemics, within their borders and across regions. The Committee would function in a similar fashion as the Counter Terrorism Committee that was established following the 9/11 terrorist attacks in the United States.
  • States should present reports on their level of preparedness to the UN Security Council. The Crisis Preparedness Committee could establish a group of experts who would conduct expert assessments of each member state’s risks and preparedness and facilitate technical assistance as required.
  • Regional bodies such as the OSCE, ASEAN and ARF, the AU, the OAS, the PIF etc could also request national reports on crisis preparedness for discussion and cooperation at the regional level.

COVID-19 has been referred to as the 9/11 of crisis preparedness and response. Just as that shocking terrorist attack shifted the world and created a series of measures to address terrorism, we now recognise our security frameworks need far more emphasis on being prepared and being resilient. Whatever has been done in the past, it is clear that was nowhere near enough and that has to change.

Case Study of Preparedness: The UK

The National Risk Register was first published in 2008 as part of the undertakings laid out in the National Security Strategy (the UK also published the Biological Security Strategy in July 2018). Now entitled the National Risk Register for Civil Emergencies it has been updated regularly to analyse the risks of major emergencies that could affect the UK in the next five years and provide resilience advice and guidance.

The latest edition - produced in 2017 when the UK had a Minister for Government Resilience and Efficiency - placed the risk of a pandemic influenza in the ‘highly likely and most severe’ category. It stood out from all the other identified risks, whereas an emerging disease (such as COVID-19) was identified as ‘highly likely but with moderate impact’.

However, much preparatory work for an influenza pandemic is the same as for COVID-19, particularly in prepositioning large stocks of PPE, readiness within large hospitals, and the creation of new hospitals and facilities.

One key issue is that the 2017 NHS Operating Framework for Managing the Response to Pandemic Influenza was dependent on pre-positioned ’just in case’ stockpiles of PPE. But as it became clear the PPE stocks were not adequate for the pandemic, it was reported that recommendations about the stockpile by NERVTAG (the New and Emerging Respiratory Virus Threats Advisory Group which advises the government on the threat posed by new and emerging respiratory viruses) had been subjected to an ‘economic assessment’ and decisions reversed on, for example, eye protection.

The UK chief medical officer Dame Sally Davies, when speaking at the World Health Organization about Operation Cygnus – a 2016 three-day exercise on a flu pandemic in the UK – reportedly said the UK was not ready for a severe flu attack and ‘a lot of things need improving’.

Aware of the significance of the situation, the UK Parliamentary Joint Committee on the National Security Strategy launched an inquiry in 2019 on ‘Biosecurity and human health: preparing for emerging infectious diseases and bioweapons’ which intended to coordinate a cross-government approach to biosecurity threats. But the inquiry had to postpone its oral hearings scheduled for late October 2019 and, because of the general election in December 2019, the committee was obliged to close the inquiry.




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Iran Crisis: How Far Does Trump’s Authority Go?

10 January 2020

Dr Leslie Vinjamuri

Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme
The legal and political boundaries of presidential power are being redefined, but the president may still be attentive to some constraints.

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Donald Trump arrives for a rally in Toledo, Ohio on 9 January. Photo: Getty Images.

On Thursday, the US House of Representatives passed a resolution affirming its authority under the War Powers Resolution Act, and reminding the president, the American people and the world that when it comes to the use of military force, Congress must be taken into account. 

President Donald Trump replied by retweeting John Bolton, his former national security advisor, who tweeted that the War Powers Act was ‘unconstitutional’, effectively dismissing Congressional efforts to rein in the president.

This round of legal Twitter diplomacy came days after the president tweeted that ‘legal notice (to Congress) is not required, but it is given nevertheless’ and that ‘should Iran strike any US person or target, the United States will quickly and fully strike back, and perhaps in a disproportionate manner.’ 

President Trump’s overt attacks on Congressional authority and disregard for the law are not normal for a US president, but legal constraints over the president’s authority to use military force have been eroding for several years.

In 1973, Congress passed the War Powers Act, requiring the president to report to Congress and acquire Congressional approval for continued overseas troop deployments. But Congressional authority over the use of military force has continued to diminish, especially since the 9/11 attacks. 

Now, Congress is pushing back – a resolution similar to that passed by the House is likely to be voted on by the Senate soon. Given the intense frustration of some senators over the president’s handling of the current conflict, this resolution may pass, though the president is still likely to veto. 

The bigger problem, of which this is one part, is the expansion of executive authority, and it predates this presidency. Many argue that executive power is greatest on matters of foreign policy, and that in this domain the US president is unconstrained. As partisanship has increased and the demands on Congress have made it harder for its members to cultivate foreign policy expertise, the power of the president has grown.

So the fact that Congress is taking active steps to check the president’s power not only on the question of impeachment, but also on foreign policy, is significant, even if the law is not likely to restrain President Trump. But Congress is also playing a long game. And its growing determination to assert its authority matters not only for this presidency, but also for the future.

Political constraints

In the short term, other constraints matter more. Even if President Trump rejects legal restraints – and shuns diplomatic pressure that might have mattered to other presidents – he is not impervious to political restraint.

Already there are signs that Trump listens to his key Republican allies in Congress. When Senator Lindsay Graham pushed back against the president’s threat to attack cultural heritage sites in Iran, and the Pentagon failed to shore up the president’s threat, the president changed his position. The threats also provoked an overwhelming response in Europe, and across the Middle East, but the president has shown that he is willing to disregard international admonishment. Not so for domestic allies.

Nor is this the first time that Senator Graham’s views have mattered. When the president announced his decision to pull troops from northeast Syria, effectively abandoning the Kurds, a key partner to the US in its fight against ISIS, Senator Graham and Senator Mitch McConnell pushed back and it mattered. 

Public opinion also matters to the president, especially Republican public opinion, and this is likely to affect the president’s next steps. Recent polls suggest that Americans feel less safe as a result of the killing of General Qassem Soleimani by a considerable margin of 55% to 24%.

But the same survey also shows that a majority of Americans support the decision to kill Soleimani. Already Vice President Mike Pence has spoken at a rally in Ohio designed to bolster support for this Presidential action.  

So what might change public opinion and will this alter the president’s future steps?

Americans are very reluctant to support further deployments of troops overseas. President Trump knows this and he has consistently stated that he seeks to pull US troops out of the Middle East.

In fact, the opposite has happened. And once again, the decision to kill General Soleimani is pulling the US further into the Middle East and putting into stark light the inconsistency of Trump’s foreign policy ambitions. In recent days, the United States has committed to sending thousands of troops to the region.

Continued US troop deployments may not play well with Trump’s base, though they currently support his Iran policy. But absent an obvious justification, this could change, so it is not surprising that this has become a rallying point for Vice President Pence.

An even greater political risk, and one that will matter to the president, is the risk to US military personnel and civilians overseas. Public support for the killing of Soleimani and increased US presence in the region is bound to dissipate if Americans are killed.

But it isn’t clear how the president will respond, and already the death of one American in the militia attack on 27 December seems to have been a critical factor in Trump’s decision to authorize the assassination of General Soleimani.  

So far, Iran’s response appears to be calibrated to avoid this kind of public backlash, and keep the door open to some sort of managed resolution of the current crisis.

But the considerable risk of miscalculation and mistakes has already been born out. A week after the killing of Soleimani, the world is tuning in to the tragic news that a civilian airliner departing Iran for Ukraine appears to have been accidentally shot down by an Iranian missile, resulting in the deaths of all 176 people on board, including 82 Iranians and 63 Canadians.

Whether the US president is constrained is a critical question for Americans, for US democracy and for the rest of the world. Trump is different, but he is not unconstrained. Steps taken by Congress along with diplomatic and political pressure mean he is still operating within boundaries. But it is clear that these boundaries are being redefined.




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The UK, US and Mauritius: Decolonization, Security, Chagos and the ICJ

Invitation Only Research Event

30 January 2020 - 8:15am to 9:15am

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

Event participants

Professor Philippe Sands QC, Professor of Law, UCL 
Richard Burt, Managing Partner, McLarty Associates
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House

The Chagos archipelago in the Indian Ocean has garnered media attention recently after the UK failed to abide by a UN deadline to return the islands to Mauritius. The US has landed in the middle of the dispute as a 1965 agreement with the UK has allowed the US to establish a military base on one of the islands, Diego Garcia, which has since become instrumental in US missions in the Asia-Pacific and the Middle East. 

In February 2019, an Advisory Opinion of the International Court of Justice (ICJ) found that the Chagos archipelago was unlawfully dismembered from Mauritius, in violation of the right to self-determination and that the United Kingdom is under an obligation to end its administration of the Chagos archipelago ‘as rapidly as possible’. The UN General Assembly subsequently voted overwhelmingly in favour of the UK leaving the islands by the end of November 2019 and the right of the former residents who were removed by the UK to return. The UK does not accept the ICJ and UN rulings and argues that the islands are needed to protect Britain from security threats while Mauritius has made clear the base can remain.

Professor Philippe Sands QC, professor of law at University College London and lead counsel for Mauritius on the ICJ case on Legal Consequences of the Separation of the Chagos archipelago from Mauritius in 1965, will be joining Ambassador Richard Burt, US chief negotiator in the Strategic Arms Reduction Talks with the former Soviet Union for a discussion on the fate of the archipelago including the future of the military base and the right of return of former residents.  

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Department/project

US and Americas Programme




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Ukraine Beyond Donbas: Is Social Cohesion at Risk?

Invitation Only Research Event

28 February 2020 - 9:30am to 1:00pm

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

Event participants

Iryna Brunova-Kalisetska, Independent Researcher, Trainer and Dialogue Facilitator
Maxim Ieligulashvili, Independent Researcher, Trainer and Dialogue Facilitator
Volodymyr Lupatsy, Co-founder, National Platform on Dialogue for Peace and Secure Reintegration; Board Member, Centre for Security and Development Research, Ukraine
Orysia Lutsevych, Research Fellow and Manager, Ukraine Forum, Chatham House

Six years after the annexation of Crimea and the start of the armed conflict in Donbas, the process of coalescing the Ukrainian society around a common civic identity remains complex. Ukraine comprises many ethno-linguistic identities, and various internal and external actors have been able to exploit old and new grievances to increase tensions at the regional and local level.

The panellists will discuss the conflict dynamics along parts of Ukraine’s international border and the line of contact with Crimea. The speakers will review the internal political, social and economic trends that cause friction and suggest ways to strengthen cohesion.

The event will build upon key findings from International Alert’s analysis of the south of Odesa, Kherson and Zakarpattia oblasts and on the reintegration of veterans in Ukraine.

This event is organized in partnership with International Alert, supported by UK aid from the UK government as part of the Peace Research Partnership programme.

 

Anna Morgan

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




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Post-Paris: Taking Forward the Global Climate Change Deal

21 April 2016

Inevitably, the compromises of the Paris Agreement make it both a huge achievement and an imperfect solution to the problem of global climate change.

Rob Bailey

Former Research Director, Energy, Environment and Resources
Shane Tomlinson
Former Senior Research Fellow, Energy, Environment and Resources

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The slogan '1.5 Degrees' is projected on the Eiffel Tower as part of the World Climate Change Conference 2015 (COP21) on 11 December 2015 in Paris, France. Photo by Getty Images.

Summary

  • The Paris Agreement, reached at COP21, was a triumph of diplomacy. The deal can be characterized as: flexible, combining a ‘hard’ legal shell and a ‘soft’ enforcement mechanism; inclusive, as it was adopted by all 196 parties to the UNFCCC and is therefore the first truly global climate deal; messy, as the bottom-up process of creating nationally determined contributions means the system is unstandardized; non-additive, as the contributions do not currently deliver the agreement’s stated long-term goal of keeping the rise in global average temperature to ‘well below 2˚C’; and dynamic, as the deal establishes a ratchet mechanism that requires more ambitious contributions every five years.
  • The next five years are critical for keeping the below 2˚C goal within reach. A ‘facilitative dialogue’ starting in 2018 will give states the opportunity to revisit their contributions in advance of the agreement entering into force in 2020. International forums, such as the G7 and G20, can play a crucial role in kickstarting these efforts.
  • The ‘coalitions of the willing’ and clubs that were launched under the Lima-Paris Action Agenda provide an innovative space for state and non-state actors to unlock transformational change. However, it is important that these groups set specific and measurable targets to ensure effective delivery of objectives.
  • The post-Paris regime implies a significant role for civil society organizations. However, in many countries the ‘safe operating space’ both for these organizations and for the media is shrinking. Expanding the capacity of civil society and the media in areas such as communications, litigation, project implementation and technical expertise will be important if they are to support the regime effectively.




s:

Randeen Thomas: The Man with the ‘Mix’

IF MIXOLOGY is artistry in motion, then consider the instruments as the canvas, the ingredients as the paint, and Randeen Thomas as the Pablo Picasso of his time, giving spirits new life. Some might be familiar with ‘The Big Belly Bartender’,...




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Densil A. Williams | COVID-19 after-shocks: Is Jamaica ready?

As Jamaica signs off on Budget 2020-2021, we are still uncertain whether we will be able to withstand the economic onslaught that will accompany the crisis in the years to come. It is clear that this pandemic is like none other that we have seen...




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Antoinette Davis: The Beauty Behind Ettenio

Everyone these days is so focused on the beauty behind hair and skincare lines that they neglect to really explore the science behind them. Creating revolutionary products that are not only innovative but eco-friendly is entrepreneur Antoinette...




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Braves notes: McCann, Soroka, Gohara

Brian McCann still laughs about what transpired as he learned the Braves were calling him up to the Majors during the 2005 season. He remembers being summoned to Brian Snitker's room, where he found the then Double-A manager eating pizza while wearing nothing more than his underwear.




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Astros' notes: Reddick, Marisnick, Dawson

Astros outfielder Josh Reddick vows to start hitting to the opposite field more this year, which is something he did well in 2017, but not '18. Reddick hit .242 with 17 homers and 47 RBIs last year after hitting .314 with 13 homers and 82 RBIs to help the Astros to the World Series title in '17.




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High Incidence of Metabolically Active Brown Adipose Tissue in Healthy Adult Humans: Effects of Cold Exposure and Adiposity

Masayuki Saito
Jul 1, 2009; 58:1526-1531
Metabolism




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Inflammatory Cytokines and the Risk to Develop Type 2 Diabetes: Results of the Prospective Population-Based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study

Joachim Spranger
Mar 1, 2003; 52:812-817
Pathophysiology




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Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents

G Perseghin
Aug 1, 1999; 48:1600-1606
Articles




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Mechanisms of Pancreatic {beta}-Cell Death in Type 1 and Type 2 Diabetes: Many Differences, Few Similarities

Miriam Cnop
Dec 1, 2005; 54:S97-S107
Section III: Inflammation and beta-Cell Death




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Estimation of Insulin Secretion Rates from C-Peptide Levels: Comparison of Individual and Standard Kinetic Parameters for C-Peptide Clearance

Eve Van Cauter
Mar 1, 1992; 41:368-377
Original Article




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Elevated Levels of Acute-Phase Proteins and Plasminogen Activator Inhibitor-1 Predict the Development of Type 2 Diabetes: The Insulin Resistance Atherosclerosis Study

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications




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Role of oxidative stress in diabetic complications: a new perspective on an old paradigm

JW Baynes
Jan 1, 1999; 48:1-9
Articles




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U.K. Prospective Diabetes Study 16: Overview of 6 Years' Therapy of Type II Diabetes: A Progressive Disease

U.K. Prospective Diabetes Study Group
Nov 1, 1995; 44:1249-1258
Perspectives in Diabetes




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Quantification of the Relationship Between Insulin Sensitivity and {beta}-Cell Function in Human Subjects: Evidence for a Hyperbolic Function

Steven E Kahn
Nov 1, 1993; 42:1663-1672
Original Article




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The Pathobiology of Diabetic Complications: A Unifying Mechanism

Michael Brownlee
Jun 1, 2005; 54:1615-1625
Banting Lecture 2004




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PPARA Polymorphism Influences the Cardiovascular Benefit of Fenofibrate in Type 2 Diabetes: Findings From ACCORD-Lipid

The cardiovascular benefits of fibrates have been shown to be heterogeneous and to depend on the presence of atherogenic dyslipidemia. We investigated whether genetic variability in the PPARA gene, coding for the pharmacological target of fibrates (PPAR-α), could be used to improve the selection of patients with type 2 diabetes who may derive cardiovascular benefit from addition of this treatment to statins. We identified a common variant at the PPARA locus (rs6008845, C/T) displaying a study-wide significant influence on the effect of fenofibrate on major cardiovascular events (MACE) among 3,065 self-reported white subjects treated with simvastatin and randomized to fenofibrate or placebo in the ACCORD-Lipid trial. T/T homozygotes (36% of participants) experienced a 51% MACE reduction in response to fenofibrate (hazard ratio 0.49; 95% CI 0.34–0.72), whereas no benefit was observed for other genotypes (Pinteraction = 3.7 x 10–4). The rs6008845-by-fenofibrate interaction on MACE was replicated in African Americans from ACCORD (N = 585, P = 0.02) and in external cohorts (ACCORD-BP, ORIGIN, and TRIUMPH, total N = 3059, P = 0.005). Remarkably, rs6008845 T/T homozygotes experienced a cardiovascular benefit from fibrate even in the absence of atherogenic dyslipidemia. Among these individuals, but not among carriers of other genotypes, fenofibrate treatment was associated with lower circulating levels of CCL11—a proinflammatory and atherogenic chemokine also known as eotaxin (P for rs6008845-by-fenofibrate interaction = 0.003). The GTEx data set revealed regulatory functions of rs6008845 on PPARA expression in many tissues. In summary, we have found a common PPARA regulatory variant that influences the cardiovascular effects of fenofibrate and that could be used to identify patients with type 2 diabetes who would derive benefit from fenofibrate treatment, in addition to those with atherogenic dyslipidemia.




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Sector groups: Increase business hours

No sooner than the Government’s announced its intention to restart the economy, private sector groups are advocating for longer working hours to fast-track recovery during the COVID-19 pandemic. In a collaborative move, the Jamaica Manufacturers...




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Nevis: No active cases of COVID-19 on island

As of May 6, officials in Nevis are reporting that there are no active cases of the deadly COVID-19 virus on the island. This was confirmed Tuesday by Premier Mark Brantley, Minister responsible for Health, in the Nevis Island Administration....




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Rotating night shift work and adherence to unhealthy lifestyle in predicting risk of type 2 diabetes: results from two large US cohorts of female nurses




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Type 2 diabetes: sweetened drinks pose greater risk than other sugary foods




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Type 2 diabetes: 5000 patients to test feasibility of “remission service”




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Diabetes: precision approach will improve outcomes, says research director




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Quality of dietary fat and genetic risk of type 2 diabetes: individual participant data meta-analysis




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A Novel Model of Diabetic Complications: Adipocyte Mitochondrial Dysfunction Triggers Massive {beta}-Cell Hyperplasia

Obesity-associated type 2 diabetes mellitus (T2DM) entails insulin resistance and loss of β-cell mass. Adipose tissue mitochondrial dysfunction is emerging as a key component in the etiology of T2DM. Identifying approaches to preserve mitochondrial function, adipose tissue integrity, and β-cell mass during obesity is a major challenge. Mitochondrial ferritin (FtMT) is a mitochondrial matrix protein that chelates iron. We sought to determine whether perturbation of adipocyte mitochondria influences energy metabolism during obesity. We used an adipocyte-specific doxycycline-inducible mouse model of FtMT overexpression (FtMT-Adip mice). During a dietary challenge, FtMT-Adip mice are leaner but exhibit glucose intolerance, low adiponectin levels, increased reactive oxygen species damage, and elevated GDF15 and FGF21 levels, indicating metabolically dysfunctional fat. Paradoxically, despite harboring highly dysfunctional fat, transgenic mice display massive β-cell hyperplasia, reflecting a beneficial mitochondria-induced fat-to-pancreas interorgan signaling axis. This identifies the unique and critical impact that adipocyte mitochondrial dysfunction has on increasing β-cell mass during obesity-related insulin resistance.




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Understanding Diabetic Neuropathy--From Subclinical Nerve Lesions to Severe Nerve Fiber Deficits: A Cross-Sectional Study in Patients With Type 2 Diabetes and Healthy Control Subjects

Studies on magnetic resonance neurography (MRN) in diabetic polyneuropathy (DPN) have found proximal sciatic nerve lesions. The aim of this study was to evaluate the functional relevance of sciatic nerve lesions in DPN, with the expectation of correlations with the impairment of large-fiber function. Sixty-one patients with type 2 diabetes (48 with and 13 without DPN) and 12 control subjects were enrolled and underwent MRN, quantitative sensory testing, and electrophysiological examinations. There were differences in mechanical detection (Aβ fibers) and mechanical pain (A fibers) but not in thermal pain and thermal detection clusters (C fibers) among the groups. Lesion load correlated with lower Aα-, Aβ-, and A-fiber but not with C-fiber function in all participants. Patients with lower function showed a higher load of nerve lesions than patients with elevated function or no measurable deficit despite apparent DPN. Longer diabetes duration was associated with higher lesion load in patients with DPN, suggesting that nerve lesions in DPN may accumulate over time and become clinically relevant once a critical amount of nerve fascicles is affected. Moreover, MRN is an objective method for determining lower function mainly in medium and large fibers in DPN.




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Troponin T Parallels Structural Nerve Damage in Type 2 Diabetes: A Cross-sectional Study Using Magnetic Resonance Neurography

Clinical studies have suggested that changes in peripheral nerve microcirculation may contribute to nerve damage in diabetic polyneuropathy (DN). High-sensitivity troponin T (hsTNT) assays have been recently shown to provide predictive values for both cardiac and peripheral microangiopathy in type 2 diabetes (T2D). This study investigated the association of sciatic nerve structural damage in 3 Tesla (3T) magnetic resonance neurography (MRN) with hsTNT and N-terminal pro-brain natriuretic peptide serum levels in patients with T2D. MRN at 3T was performed in 51 patients with T2D (23 without DN, 28 with DN) and 10 control subjects without diabetes. The sciatic nerve’s fractional anisotropy (FA), a marker of structural nerve integrity, was correlated with clinical, electrophysiological, and serological data. In patients with T2D, hsTNT showed a negative correlation with the sciatic nerve’s FA (r = –0.52, P < 0.001), with a closer correlation in DN patients (r = –0.66, P < 0.001). hsTNT further correlated positively with the neuropathy disability score (r = 0.39, P = 0.005). Negative correlations were found with sural nerve conduction velocities (NCVs) (r = –0.65, P < 0.001) and tibial NCVs (r = –0.44, P = 0.002) and amplitudes (r = –0.53, P < 0.001). This study is the first to show that hsTNT is a potential indicator for structural nerve damage in T2D. Our results indirectly support the hypothesis that microangiopathy contributes to structural nerve damage in T2D.




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Human conflict and ecosystem services: finding the environmental price of warfare

2 July 2014 , Volume 90, Number 4

Robert A. Francis and Krishna Krishnamurthy




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Addressing Resource Conflicts: Working Towards More Effective Resolution of Natural Resource Disputes

Invitation Only Research Event

26 June 2014 - 9:00am to 5:00pm

Chatham House, London

Disputes over resources are a persistent challenge to international peace and security. Natural resources (such as oil, natural gas, minerals, timber and water) are a major source of national income for many countries and, alongside land, are essential to the livelihoods of many millions of people. There is a growing recognition among researchers and decision-makers that in many fragile states disputes over these resources have fed into, and underpinned, violent conflict and instability. 

Although international engagement in national resource disputes is not always desirable or feasible, where it is necessary and possible to support, supplement (or even substitute) national dispute resolution processes it is important to think through the parameters of such action: Who gets involved? With what financial resources? When does an intervention begin? How do they act? 

This one-day roundtable will bring together around 30 experts from policy, academia and business to discuss these questions and more.

The event will be held under the Chatham House Rule. Attendance is by invitation only.

Event attributes

Chatham House Rule

Owen Grafham

Manager, Energy, Environment and Resources Programme
+44 (0)20 7957 5708




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Methodology for Estimating Levels of Illegal Timber- and Paper-sector Imports: Estimates for China, France, Japan, the Netherlands, the UK, the US and Vietnam

25 November 2014

This paper accompanies a series of assessments on China, France, Japan, the Netherlands, the UK, the US and Vietnam, providing details on how the estimates of the level of illegality of imports of wood-based products into those countries were derived.

Alison Hoare

Senior Research Fellow, Energy, Environment and Resources Programme

This paper accompanies a series of Chatham House assessments on China, France, Japan, the Netherlands, the UK, the US and Vietnam and provides details on how the estimates of the level of illegality of imports of wood-based products into those countries were derived. The assessments are part of a research project that monitored levels of illegal logging and related trade in selected consumer, producer and processing countries in order to evaluate the effectiveness of efforts to tackle this problem.

The paper describes the methodology for estimating the levels of wood-based products at high risk of illegality that are being imported into consumer and processing countries. The methodology was developed in order to provide quantitative estimates of the scale of such imports and to assess how they have changed over time. The figures adopted for the assessments are based on the best available evidence; but, given the challenges of quantifying levels of illegal logging and the limited information available for some countries, they should not be regarded as definitive. Rather, they indicate the likely levels of illegality and, perhaps more important, how they may have changed over time.




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Resource Development in Fragile and Conflict-Affected States: Can it Promote Peace?

Research Event

30 September 2014 - 1:30pm to 4:45pm

Chatham House, London

The discovery of valuable natural resources such as hydrocarbons or minerals in conflict-affected states or disputed regions can be a double-edged sword. While economic growth may help overcome conflict and consolidate peace, much of the academic literature links the economic, social and environmental impacts of resource development with an increased risk of violent conflict between or within fragile states. 

Recently however, the role of business in advancing peace has emerged as a topic of increasing discussion in academia and in forums such as the UN Global Compact. Resource development has also become a key objective for donor development strategies in fragile states such as Afghanistan, Somalia and Myanmar, on the assumption that extractive sector development can contribute to stability and security. 

This event will gather key stakeholders from business and policy to investigate if and where natural resource development has contributed to peace-building, built cooperation among stakeholders or helped to resolve, rather than exacerbate, tensions. If so, it will endeavour to draw out common, replicable lessons of what made these developments successful from a peace-building perspective.

The event will be held under the Chatham House Rule.

Event attributes

Chatham House Rule




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Cartels and Competition in Minerals Markets: Challenges for Global Governance

19 December 2014

This research paper sets out recommendations for enhanced dialogue and intensified international cooperation that could significantly improve the functioning of global mineral markets.

Felix Preston

Former Senior Research Fellow and Deputy Research Director, Energy, Environment and Resources

Siân Bradley

Research Fellow, Energy, Environment and Resources Programme

Jaakko Kooroshy

Former Chatham House Expert
The purpose of this research paper is to identify and analyse the key policy challenges associated with anti-competitive practices in international metals and minerals markets.

Recommendations

Enhanced dialogue and intensified international cooperation in four areas could significantly improve the functioning of global mineral markets:

  1. Deal with the last remnants of producer-country cartels 
    Consumer countries should make a publicly visible case that in an age of interdependence and global supply chains, any remaining forms of producer-country cartels are an anachronism. Given limited means to coerce governments to stop supporting the last remaining mineral cartels in potash, a ‘naming and shaming’ approach in key forums such as the Group of Twenty (G20) and the Organization for Economic Cooperation and Development (OECD) is likely to be most effective. Such action could be initiated by the three largest potash importers China, India and Brazil, and should seek support from others such as the EU and Japan.
     
  2. Prevent damaging export restrictions through win-win arrangements
    WTO litigation against export restrictions is unlikely to be a silver bullet and in the short term cooperative policy dialogues, such as those pursued by the OECD, offer the best prospects for concrete results. Such dialogues should also be initiated by major emerging economies and could focus on providing incentives such as investment packages or technology-sharing to entice producer countries to abstain from imposing restrictions. Consumers should continue to push for more specific and stricter WTO rules on export restrictions. Japan, the EU and the US should seek to include similar measures in regional trade negotiations.
     
  3. Strengthen cooperation among regulators on clandestine private cartels and other anti-competitive practices 
    Concerted action will be required by governments to tackle anti-competitive practices such as clandestine cartels, price-fixing and territorial agreements. Key regulators, such as those in the EU and China, should expand collection and sharing of data and best practice on anti-trust enforcement in minerals markets. In key cases they could also coordinate prosecution. Sustained investment in institutional capacity is required in many emerging economies; this should be supported through bilateral cooperation and via regional forums. Governments should also resuscitate the stalled negotiations on the WTO’s role in competition policy.
     
  4. Enhance governance for transnational market platforms and pricing mechanisms
    The responsibility to regulate key nodes in global minerals markets will remain in the hands of national bodies, but coordination is vital given interconnected global markets. International organizations and regulators should strengthen structural cooperation and exchange in the area of physical markets and with greater involvement of emerging economies. An informal high-level forum on regulating physical markets could reinvigorate debate, foster new perspectives and stimulate new partnerships. Governments in key consumer countries should also give their national regulators a clear mandate in minerals markets.




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The Impact of Mining on Forests: Information Needs for Effective Policy Responses

Invitation Only Research Event

3 June 2015 - 9:00am to 6:00pm

Chatham House, London

While there is much anecdotal information about the impact of mining on forests, no comprehensive review of minerals as a forest risk commodity has yet been undertaken. Indications are that mining activities are an important driver of deforestation in many countries, and that the impact of mineral extraction on forest resources is likely to increase with growing global demand for minerals. 

This event will discuss the state of knowledge on the impact of mining on forests, identify the available policy tools aimed at supporting sustainable supply chains, and determine the data needs to facilitate improved monitoring, control and regulation of the sector. 

Attendance at this event is by invitation only.

Adelaide Glover

Digital Coordinator, Energy, Environment and Resources Programme




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Reducing Deforestation in Agricultural Commodity Supply Chains: Using Public Procurement Policy

2 September 2015

This paper explores the potential of using public procurement policy to promote the uptake of sustainable food products in order to reduce imports of agricultural products associated with deforestation.

 

Duncan Brack

Associate Fellow, Energy, Environment and Resources Programme

20150827AgricultureDeforestationBrack.jpg

Workers sort cocoa fruits near the Mendoa Chocolates plant in the state of Bahia near Ilheus, Brazil. Photo: Getty Images.

Summary

  • Procurement policy has been used effectively to exclude illegal and unsustainable timber from consumer-country markets.
  • As the public sector is a major purchaser of food and catering services for schools, nurseries, hospitals, care homes, canteens, prisons and the military, public procurement policies in this area clearly have the potential to promote the uptake of sustainable products not associated with deforestation.
  • Many public authorities, particularly at local and regional level, already have a procurement policy for food; in principle, criteria for sustainable production could be incorporated relatively easily.
  • Some products – particularly palm oil, cocoa, coffee and tea – are better suited than others to this approach; for all these products, voluntary certification initiatives currently under way could provide identification mechanisms on which procurement policies could rest.
  • Other commodities may not be as suited to procurement policy, and it may be more effective to use other regulations; this applies particularly to soy, for which biofuel regulations are likely to have a bigger impact.
  • In cases in which private-sector initiatives are under way to achieve 100 per cent sustainable imports (such a target has been set for palm oil in several countries), procurement policy may be unnecessary. In other cases, the adoption of a new procurement policy could serve as the spur to a private-sector initiative. 




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Agricultural Commodity Supply Chains: Trade, Consumption and Deforestation

28 January 2016

Private-sector commitments and government policies, a loss of support for biofuels, and health concerns over the consumption of palm oil and beef, are factors that may help to restrict the further expansion of agricultural land into forest areas.

Duncan Brack

Associate Fellow, Energy, Environment and Resources Programme

Laura Wellesley

Research Fellow, Energy, Environment and Resources Programme

Adelaide Glover, Project Coordinator, Forest Governance and Natural Resources

2016-01-28-agricultural-commodity-supply-chain.jpg

An employee arranges packages of instant ramen noodles a store in Seoul, South Korea. Photo via Getty Images.
  • Clearance of forests for agriculture is a major cause of deforestation worldwide; the three most significant commodities in this regard are palm oil, soy and beef, which between them accounted for an estimated 76 per cent of the deforestation associated with agriculture in 1990–2008. International markets are an important driver of demand, particularly for palm oil and soy.
  • Global production of palm oil has grown strongly for several decades, more than doubling over the period 2000–13. Indonesia and Malaysia between them account for more than 80 per cent of palm oil production, and are likely to continue to dominate world exports. The European Union (EU), India and China are the main consumers, importing almost 60 per cent of the market; EU demand is driven significantly by biofuel policy, while India and China use palm oil mainly as a cooking oil and in processed foods.
  • Global production of soybeans has roughly doubled since 2000, and the expansion of output has been particularly rapid in South America; Brazil and Argentina accounted for almost 50 per cent of global production in 2013. Overwhelmingly the main importer is China (which took 43 per cent of all soy imports in 2014), mainly for animal feed for its growing meat industry. The EU is the second largest importer, using soy for animal feed and biofuel.
  • In contrast, consumption and production of beef has grown only slowly. Major producers are the US, Brazil, the EU and China; principal exporters are Brazil, India, Australia and the US. The US and the EU are still major consumers, although – as in most developed countries – consumption is falling slightly; other significant consumers include Brazil, India, Pakistan and China. Russia and Japan are also significant importers.
  • Three main factors underlie the growth in both consumption and production of palm oil and soy: population growth; changing dietary preferences; and policy support for biofuels. The first two are just as relevant to beef. Continued growth in world population and the expansion of the global middle class, with accompanying higher consumption levels of processed food and meat, will continue to drive demand upwards – strongly for palm oil and soy, more weakly for beef. Given the difficulty of increasing yields, particularly in developing countries, the further expansion of agricultural land into forest areas is inevitable. None the less, three other factors may restrict this growth: the private-sector commitments and government policies that are being developed with the aim of decoupling agricultural production from deforestation; a loss of support for biofuels, most notably in the EU; and health concerns, particularly over the consumption of palm oil and beef.

 




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First-in-Humans Imaging with 89Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of 89Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. Methods: The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of 89Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1–2, 6–8, 24, 48, and 96–144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Results: 89Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time–activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24–48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most 89Zr-IAB22M2C–positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Conclusion: 89Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell–rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.