ac

The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism

Gijs den Besten
Sep 1, 2013; 54:2325-2340
Reviews




ac

Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth

MS Brown
Jul 1, 1980; 21:505-517
Reviews




ac

Marked reduction in bile acid synthesis in cholesterol 7{alpha}-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia

Margrit Schwarz
Sep 1, 1998; 39:1833-1843
Articles




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Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis

Chi-Liang Eric Yen
Nov 1, 2008; 49:2283-2301
Thematic Reviews




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Gene expression regulation by retinoic acid

James E. Balmer
Nov 1, 2002; 43:1773-1808
Reviews




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Intracellular cholesterol transport

CJ Fielding
Aug 1, 1997; 38:1503-1521
Reviews




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Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics

Vitali Matyash
May 1, 2008; 49:1137-1146
Methods




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Perilipin is located on the surface layer of intracellular lipid droplets in adipocytes

EJ Blanchette-Mackie
Jun 1, 1995; 36:1211-1226
Articles




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Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression

K Schoonjans
May 1, 1996; 37:907-925
Reviews




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Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E

Robert W. Mahley
Jan 1, 1999; 40:1-16
Reviews




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Bile salt biotransformations by human intestinal bacteria

Jason M. Ridlon
Feb 1, 2006; 47:241-259
Reviews




ac

Direct transesterification of all classes of lipids in a one-step reaction

G Lepage
Jan 1, 1986; 27:114-120
Articles




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Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride--methanol

William R. Morrison
Oct 1, 1964; 5:600-608
Articles




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Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans

Saverio Cinti
Nov 1, 2005; 46:2347-2355
Research Articles




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The plasma lecithin:cholesterol acyltransferase reaction

John A. Glomset
Mar 1, 1968; 9:155-167
Reviews




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Partisanship Meets Trump’s Impeachment

19 December 2019

Dr Lindsay Newman

Senior Research Fellow, US and the Americas Programme
History shows that if those pushing for impeachment and removal want to succeed, they need to drive up popular support for a senate conviction.

GettyImages-1189454843.jpg

Opposing protests during the House of Representatives debate on whether to charge President Donald Trump with two articles of impeachment. Photo by Sarah Silbiger/Getty Images.

The vote to impeach Donald Trump holds almost no surprises - on both the abuse of power and obstruction of congress articles, the votes were split entirely on party lines with nearly all the majority-led House Democrats but not a single Republican voting to impeach Trump.

However, this ‘pre-ordained’ outcome of the House impeachment inquiry does serve to highlight that the US is in the midst of a hyper-partisan political moment. Policy gridlock has led to two government shutdowns during Donald Trump’s presidency, with one further budgetary fight narrowly avoided.

With a few notable exceptions (such as USMCA), policy areas that lend themselves to bipartisanship - including infrastructure and drug pricing - have seen very little progress under divided congressional chambers. Party identification can now be overlaid with the cable news channel one watches or the newspaper one reads.

Impeachment now moves to the Senate for a trial, requiring a two-thirds majority of the Republican-led senate (or 67 senators) for a conviction. Given the congressional partisanship we are seeing, the baseline scenario continues to be that the senate will not vote to convict Trump and remove him from office - despite much being made of how many senators are likely to vote for a Senate conviction.

Why public opinion could be crucial

There is another story to keep a close eye on. The number to track is 47.2 – the current polling average of public support for Trump’s impeachment. Polling averages from the end of September 2019 (before the hearings began, but after House Speaker Nancy Pelosi announced a formal inquiry) had 49.4% supporting impeachment versus 47.2% this week.

Here’s why this number matters. If those pushing for impeachment and removal are unable to drive popular support across a critical threshold level, then those against impeachment and removal are not going to abandon the president and vote for a senate conviction. With Trump consistently polling in the low 40s on job approval, but in the high 80s/low 90s within the Republican party, this means Republican congress members concerned about re-election are extremely hesitant to distance themselves from him without a clear mandate from the domestic public. 

A tale of the two most recent presidents to face impeachment underscores this point. Gallup polling claimed 58% of adults supported impeaching and removing President Richard Nixon from office in August 1974, whereas only 35% of the public supported impeaching President Bill Clinton in December 1998, the month he was impeached.

Given the respective outcomes of those two impeachments, it suggests public support for impeachment and removal needs to increase well beyond the current 47.2%, to avoid the foregone conclusion of acquittal in the Senate (even if there are signs of the tide moving in the opposite direction with those against impeachment overtaking support for the first time in December).   

What does this mean for Democrats?

In the short term, if the Democrats want to make inroads into the hearts and minds of those across the partisan gulf, it will be critical to secure senate testimony from those in Trump’s inner circle at the time of the Ukrainian affair.

After Trump ordered individuals with first-hand knowledge of the administration’s efforts vis-à-vis Ukraine not to testify, House investigators were unable to call many witnesses with direct evidence (which in fact left the House testimony exposed to Republican claims of hearsay). With Trump impeached, more of the public is likely to tune in to the senate proceedings, and direct evidence by inner circle administration officials required to testify presents an opportunity to move public opinion.

House speaker Nancy Pelosi recognizes how crucial the procedures and participants for the senate trial will be, and has said she could delay sending the articles of impeachment to the senate as leverage for a 'fair trial'.

Democrats also have to consider how an impeachment inquiry that - at least from this vantage point - does not end in a conviction of the president plays out for the 2020 election campaign, especially if this also likely means that public opinion - and certainly Republican-party views - of Trump have not shifted.




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US 2020: State of the Union and State of the Race

Corporate Members Event Nominees Breakfast Briefing Partners and Major Corporates

11 March 2020 - 8:00am to 9:15am

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

Event participants

Dr Lindsay Newman, Senior Research Fellow, US and the Americas Programme, Chatham House
Chair: Dr Leslie Vinjamuri, Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme, Chatham House

The US is eight months out from consequential presidential and congressional elections. Since his election in 2016, US President Donald Trump has presided over economic expansion and record unemployment rates following a 2017 tax overhaul and deregulation policies. Trump’s approval rating is at the highest level of his presidency, while on the Democratic side, the once-wide field is in a process of narrowing as intra-party ideological differences persist.
 
As we look ahead to the presidential elections in November 2020, Dr Lindsay Newman will reflect on Donald Trump’s presidency, the state of the 2020 election and preview the potential directions of travel ahead under a Trump 2.0 or a Democratic administration. How can we understand the health of Trump’s presidency post-impeachment and post-State of the Union address? What will Trump’s likely foreign policy priorities be ahead of his re-election bid including prospects for a US-UK or a US-Europe trade deal? And, across the aisle, how can we understand the Democratic primary so far and how are the Democrats positioned going into the general election? 
 

This event is only open to Major Corporate Member and Partner organizations of Chatham House. If you would like to register your interest, please RSVP to Linda Bedford. We will contact you to confirm your attendance.

To enable as open a debate as possible, this event will be held under the Chatham House Rule.


COVID-19
This event is proceeding as scheduled, as are other Chatham House events, in accordance with the advice from the UK Government, Foreign and Commonwealth Office and Public Health England. However, we are closely monitoring the spread of COVID-19 and will send updates to attendees as the situation warrants. 
In the meantime, in line with the official advice for returning travellers or visitors to the UK from specified countries and areas (see guidance here), we ask that:

  • If you have travelled from Category 1 countries/areas, you refrain from attending the event even if asymptomatic (i.e. even if you are showing no symptoms);
  • If you have travelled from Category 2 countries/areas, you refrain from attending the event should you develop symptoms.

If you fall under one of these affected categories and have any questions, please call +44 (0)207 314 3638 or email lbedford@chathamhouse.org

 

Event attributes

Chatham House Rule

Members Events Team




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Exploring the Obstacles and Opportunities for Expanded UK-Latin American Trade and Investment

Invitation Only Research Event

14 January 2020 - 8:30am to 11:00am

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

Trade and investment between the UK and Latin America is woefully underdeveloped. Latin America’s agricultural powerhouses Brazil and Argentina only accounted for a total of 1.6% of the UK’s agricultural market across eight sectors in 2018, all of those areas in which Argentina and Brazil have substantial comparative advantages. 

Conversely, UK exports to the large Latin American economies remain far below their potential.  To cite a few examples, in 2018 in the electrical equipment sector, the UK only exported $95.7 million of those products to Brazil, making the ninth largest economy in the world only the 42nd export market for those goods from the UK; Mexico only imported $91.4 million of UK-made electrical goods, placing it directly behind Brazil as UK’s market for those goods.

As we look to the future, any improvement to the relationship will depend on two factors: 1) how the UK leaves the EU and 2) whether Latin American agricultural producers can improve their environmental practices and can meet the production standards established by the EU and likely maintained by a potential post-Brexit Britain.

In the first meeting of the working group,  Chatham House convened a range of policymakers, practitioners and academics to explore this topic in depth, identify the key issues driving this trend, and begin to consider how improvements might best be made. Subsequent meetings will focus on specific sectors in commerce and investment.

We would like to thank BTG Pactual, Cairn Energy plc, Diageo, Equinor, Fresnillo Management Services, HSBC Holdings plc and Wintershall Dea for their generous support of the Latin America Initiative.

Event attributes

Chatham House Rule

US and Americas Programme




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Virtual Roundtable: Tectonic Plates of 2020 – Developments in the US Presidential Race

Invitation Only Research Event

18 March 2020 - 1:00pm to 1:45pm

Event participants

John Zogby, Founder and Senior Partner, John Zogby Strategies
Chair: Dr Lindsay Newman, Senior Research Fellow, US and Americas Programme, Chatham House

This event is part of the Inaugural Virtual Roundtable Series on the US, Americas and the State of the World and will take place virtually only. Participants should not come to Chatham House for these events.

US and Americas Programme




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Virtual Roundtable: The Economic Impact of Coronavirus

Invitation Only Research Event

23 March 2020 - 1:00pm to 2:00pm

Event participants

Megan Greene, Dame DeAnne Senior Academy Fellow in International Relations, Chatham House; Senior Fellow, Harvard Kennedy School
Lord Jim O'Neill, Chairman, Chatham House
Chair: Creon Butler, Director, Global Economy and Finance, Chatham House

This event is part of the Inaugural Virtual Roundtable Series on the US, Americas and the State of the World and will take place virtually only.  Participants should not come to Chatham House for these events.

Department/project

US and Americas Programme




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Webinar: Director's Briefing – Democracy in the Americas

Corporate Members Event Webinar Partners and Major Corporates

30 April 2020 - 1:00pm to 2:00pm

Online

Event participants

Luis Almagro, Secretary General, Organization of American States (OAS); Foreign Minister, Uruguay (2010-15)
Respondent: Dr Elena Lazarou, Associate Fellow, US and the Americas Programme, Chatham House
Respondent: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House
Chair: Dr Robin Niblett, Director and Chief Executive, Chatham House

As governments in the Americas grapple with the economic and health emergencies posed by COVID-19, the region continues to face socioeconomic and political challenges reflected in the protests that erupted in many countries in 2019. According to an annual survey by Latinóbarometro, of 18 countries across Latin America, trust in government dropped from 45 per cent in 2009 to 22 per cent in 2018, and those expressing dissatisfaction with democracy has increased from 51 per cent to 71 per cent. 

Recently re-elected to a new term, Luis Almagro, secretary general of the Organization of American States, will reflect on the state of democracy in the Americas. What are the greatest threats and opportunities to democratic governance and political participation in the region? How can multilateral organizations and states defend democratic institutions and human rights in a changing global environment? To what extent might the ongoing COVID-19 pandemic provide leaders with an opportunity to undemocratically consolidate power? Or, conversely, might the crisis spark a new understanding of the social contract between states and governed and greater consensus around national policies and leadership?  

This event is only open to Major Corporate Member and Partner organizations and selected giving circles of Chatham House. If you'd like to attend, please RSVP to lbedford@chathamhouse.org.




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Webinar: COVID-19 and the Impact on Latin American Migration

Research Event

14 May 2020 - 3:00pm to 4:00pm
Add to Calendar

Ambassador Arturo Sarukhan, Associate Fellow, US and the Americas Programme, Chatham House; Mexican Ambassador to the US, 2007 - 13
Professor Anita Isaacs, Benjamin R. Collins Professor of Social Sciences, Haverford College
Chair: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House

The US government recently announced restrictions on immigration, stating the new measures were necessary due to COVID-19 and the effect the pandemic has had on the US economy. But what is the role of immigrants in the essential official and unofficial services in the COVID-19 stay-at-home era? How is COVID-19 affecting immigration from Central America and Mexico? 

Separately, there have also been instances of outbreaks among detainees in US Immigration and Customs Enforcement centers and claims that immigrants who are returning to Guatemala are spreading the virus. How have US immigration policies affected infection rates in Central America and Mexico and among its citizens?

Arturo Sarukhan, Mexican Ambassador to the US from 2007 - 13, and Anita Isaacs, Benjamin R. Collins Professor of Social Sciences, Haverford College, will join us to discuss the impact COVID-19 is having on migrants.

Chatham House would like to thank BTG Pactual, Cairn Energy plc, Diageo plc, Equinor, Fresnillo Management Services, HSBC Holdings plc and Wintershall Dea for their generous support of the Latin America Initiative.

This event is scheduled to take place from 15:00 – 16:00 BST.

US and Americas Programme




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Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact [Neurobiology]

Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals.




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ABC transporters control ATP release through cholesterol-dependent volume-regulated anion channel activity [Signal Transduction]

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.




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S-Palmitoylation of the sodium channel Nav1.6 regulates its activity and neuronal excitability [Cell Biology]

S-Palmitoylation is a reversible post-translational lipid modification that dynamically regulates protein functions. Voltage-gated sodium channels are subjected to S-palmitoylation and exhibit altered functions in different S-palmitoylation states. Our aim was to investigate whether and how S-palmitoylation regulates Nav1.6 channel function and to identify S-palmitoylation sites that can potentially be pharmacologically targeted. Acyl-biotin exchange assay showed that Nav1.6 is modified by S-palmitoylation in the mouse brain and in a Nav1.6 stable HEK 293 cell line. Using whole-cell voltage clamp, we discovered that enhancing S-palmitoylation with palmitic acid increases Nav1.6 current, whereas blocking S-palmitoylation with 2-bromopalmitate reduces Nav1.6 current and shifts the steady-state inactivation in the hyperpolarizing direction. Three S-palmitoylation sites (Cys1169, Cys1170, and Cys1978) were identified. These sites differentially modulate distinct Nav1.6 properties. Interestingly, Cys1978 is exclusive to Nav1.6 among all Nav isoforms and is evolutionally conserved in Nav1.6 among most species. Cys1978 S-palmitoylation regulates current amplitude uniquely in Nav1.6. Furthermore, we showed that eliminating S-palmitoylation at specific sites alters Nav1.6-mediated excitability in dorsal root ganglion neurons. Therefore, our study reveals S-palmitoylation as a potential isoform-specific mechanism to modulate Nav activity and neuronal excitability in physiological and diseased conditions.




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Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors [Neurobiology]

Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development.




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Reactive dicarbonyl compounds cause Calcitonin Gene-Related Peptide release and synergize with inflammatory conditions in mouse skin and peritoneum [Molecular Bases of Disease]

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.




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

Research Event

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

Event participants

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

Hanna Desta

Programme Assistant, Africa Programme




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Webinar: COVID-19 and the Impact on Latin American Migration

Research Event

14 May 2020 - 3:00pm to 4:00pm
Add to Calendar

Ambassador Arturo Sarukhan, Associate Fellow, US and the Americas Programme, Chatham House; Mexican Ambassador to the US, 2007 - 13
Professor Anita Isaacs, Benjamin R. Collins Professor of Social Sciences, Haverford College
Chair: Dr Christopher Sabatini, Senior Research Fellow for Latin America, US and the Americas Programme, Chatham House

The US government recently announced restrictions on immigration, stating the new measures were necessary due to COVID-19 and the effect the pandemic has had on the US economy. But what is the role of immigrants in the essential official and unofficial services in the COVID-19 stay-at-home era? How is COVID-19 affecting immigration from Central America and Mexico? 

Separately, there have also been instances of outbreaks among detainees in US Immigration and Customs Enforcement centers and claims that immigrants who are returning to Guatemala are spreading the virus. How have US immigration policies affected infection rates in Central America and Mexico and among its citizens?

Arturo Sarukhan, Mexican Ambassador to the US from 2007 - 13, and Anita Isaacs, Benjamin R. Collins Professor of Social Sciences, Haverford College, will join us to discuss the impact COVID-19 is having on migrants.

Chatham House would like to thank BTG Pactual, Cairn Energy plc, Diageo plc, Equinor, Fresnillo Management Services, HSBC Holdings plc and Wintershall Dea for their generous support of the Latin America Initiative.

This event is scheduled to take place from 15:00 – 16:00 BST.

US and Americas Programme




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Coronavirus Vaccine: Available For All, or When it's Your Turn?

4 May 2020

Professor David Salisbury CB

Associate Fellow, Global Health Programme
Despite high-level commitments and pledges to cooperate to ensure equitable global access to a coronavirus vaccine, prospects for fair distribution are uncertain.

2020-05-04-Vaccine-COVID-Brazil

Researcher in Brazil working on virus replication in order to develop a vaccine against the coronavirus. Photo by DOUGLAS MAGNO/AFP via Getty Images.

When the H1N1 influenza pandemic struck in 2009, some industrialized countries were well prepared. Many countries’ preparedness plans had focused on preparing for an influenza pandemic and based on earlier alerts over the H5N1 ‘bird flu’ virus, countries had made advanced purchase or ‘sleeping’ contracts for vaccine supplies that could be activated as soon as a pandemic was declared. Countries without contracts scrambled to get supplies after those that already had contracts received their vaccine.

Following the 2009 pandemic, the European Union (EU) developed plans for joint-purchase vaccine contracts that any member state could join, guaranteeing the same price per dose for everyone. In 2009, low-income countries were unable to get the vaccine until manufacturers agreed to let 10 per cent of their production go to the World Health Organization (WHO).

The situation for COVID-19 could be even worse. No country had a sleeping contract in place for a COVID-19 vaccine since nobody had anticipated that the next pandemic would be a coronavirus, not an influenza virus. With around 80 candidate vaccines reported to be in development, choosing the right one will be like playing roulette.

These candidates will be whittled down as some will fail at an early stage of development and others will not get to scale-up for manufacturing. All of the world’s major vaccine pharmaceutical companies have said that they will divert resources to manufacture COVID-19 vaccines and, as long as they choose the right candidate for production, they have the expertise and the capacity to produce in huge quantities.

From roulette to a horse race

Our game now changes from roulette to a horse race, as the probability of winning is a matter of odds not a random chance. Countries are now able to try to make contracts alone or in purchasing consortia with other states, and with one of the major companies or with multiple companies. This would be like betting on one of the favourites.

For example, it has been reported that Oxford University has made an agreement with pharmaceutical company AstraZeneca, with a possibility of 100 million doses being available by the end of 2020. If the vaccine works and those doses materialize, and are all available for the UK, then the UK population requirements will be met in full, and the challenge becomes vaccinating everyone as quickly as possible.

Even if half of the doses were reserved for the UK, all those in high-risk or occupational groups could be vaccinated rapidly. However, as each major manufacturer accepts more contracts, the quantity that each country will get diminishes and the time to vaccinate the at-risk population gets longer.

At this point, it is not known how manufacturers will respond to requests for vaccine and how they will apportion supplies between different markets. You could bet on an outsider. You study the field and select a biotech that has potential with a good production development programme and a tie-in with a smaller-scale production facility.

If other countries do not try to get contracts, you will get your vaccine as fast as manufacturing can be scaled up; but because it is a small manufacturer, your supplies may take a long time. And outsiders do not often win races. You can of course, depending on your resources, cover several runners and try to make multiple contracts. However, you take on the risk that some will fail, and you may have compromised your eventual supply.

On April 24, the WHO co-hosted a meeting with the president of France, the president of the European Commission and the Bill & Melinda Gates Foundation. It brought together heads of state and industry leaders who committed to ‘work towards equitable global access based on an unprecedented level of partnership’. They agreed ‘to create a strong unified voice, to build on past experience and to be accountable to the world, to communities and to one another’ for vaccines, testing materials and treatments.

They did not, however, say how this will be achieved and the absence of the United States was notable. The EU and its partners are hosting an international pledging conference on May 4 that aims to raise €7.5 billion in initial funding to kick-start global cooperation on vaccines. Co-hosts will be France, Germany, Italy, the United Kingdom, Norway and Saudi Arabia and the priorities will be ‘Test, Treat and Prevent’, with the latter dedicated to vaccines.

Despite these expressions of altruism, every government will face the tension between wanting to protect their own populations as quickly as possible and knowing that this will disadvantage poorer countries, where health services are even less able to cope. It will not be a vote winner to offer a share in available vaccine to less-privileged countries.

The factories for the biggest vaccine manufacturers are in Europe, the US and India. Will European manufacturers be obliged by the EU to restrict sales first to European countries? Will the US invoke its Defense Production Act and block vaccine exports until there are stocks enough for every American? And will vaccine only be available in India for those who can afford it?

The lessons on vaccine availability from the 2009 influenza pandemic are clear: vaccine was not shared on anything like an equitable basis. It remains to be seen if we will do any better in 2020.




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Webinar: Can Responsible Behaviour in Cyberspace Be Achieved?

Members Event Webinar

26 May 2020 - 5:00pm to 6:00pm
Add to Calendar

Online

Carmen Gonsalves, Head, International Cyber Policy, Ministry of Foreign Affairs, Netherlands
Suzanne Spaulding, Senior Adviser for Homeland Security, Center for Strategic and International Studies
Chair: Joyce Hakmeh, Senior Research Fellow, International Security Programme and Co-Editor, Journal of Cyber Policy, Chatham House

Over the past couple of decades, cyberspace has evolved to become a truly global digital communication space. Managed by a multitude of state and non-state actors, it has enabled a huge range of positive innovations and developments. However, it has also become an arena of intense international competition and rivalry – a reflection of its increasing economic and political importance and broader geopolitical tensions. Despite a number of efforts and some progress in the United Nations and other forums, there are still disagreements on key issues between major powers on how to achieve responsible behaviour in cyberspace.

In light of this, the panel will explore how state and non-state actors can work together to encourage responsible behaviour in cyberspace. What challenges do various actors face in implementing agreed upon norms and principles? Is the existing global model for reaching an agreement a non-starter? What are the remaining challenges around attribution, accountability and enforcement? And what is the role for civil society, the private sector and NGOs in this debate?

This event is for Chatham House members only. Not a member? Find out more.




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Webinar: Weekly COVID-19 Pandemic Briefing – Vaccines

Members Event Webinar

13 May 2020 - 10:00am to 10:45am
Add to Calendar

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

Professor David Heymann CBE, Distinguished Fellow, Global Health Programme, Chatham House; Executive Director, Communicable Diseases Cluster, World Health Organization (1998-03)
Professor David Salisbury CB, Associate Fellow, Global Health Programme, Chatham House; Director of Immunization, Department of Health, London (2007-13)

Chair: Emma Ross, Senior Consulting Fellow, Global Health Programme, Chatham House

As countries grapple with how best to tackle the COVID-19 pandemic and the reverberations it is sending through their societies and economies, scientific understanding of how the virus is behaving, and what measures might best combat it, continues to advance. This briefing will focus on the progress towards and prospects for a coronavirus vaccine, exploring the scientific considerations, the production, distribution and allocation challenges as well as the access politics.

Join us for the eighth in a weekly series of interactive webinars on the coronavirus with Professor David Heymann and special guest, Professor David Salisbury, helping us to understand the facts and make sense of the latest developments in the global crisis. With 80 candidate vaccines reported to be in development, how will scientists and governments select the 'right' one? What should be the role of global leadership and international coordination in the development and distribution of a new vaccine? And can equitable access be ensured across the globe?

Professor Heymann is a world-leading authority on infectious disease outbreaks. He led the World Health Organization’s response to SARS and has been advising the organization on its response to the coronavirus.

Professor Salisbury was director of immunization at the UK Department of Health from 2007 to 2013. He was responsible for the national immunization programme and led the introduction of many new vaccines. He previously chaired the WHO’s Strategic Advisory Group of Experts on Immunization and served as co-chair of the Pandemic Influenza group of the G7 Global Health Security Initiative.

This event will be livestreamed.




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Accountability, denial and the future-proofing of British torture

7 May 2020 , Volume 96, Number 3

Ruth Blakeley and Sam Raphael

When powerful liberal democratic states are found to be complicit in extreme violations of human rights, how do they respond and why do they respond as they do? Drawing on the example of the United Kingdom's complicity in torture since 9/11, this article demonstrates how reluctant the UK has been to permit a full reckoning with its torturous past. We demonstrate that successive UK governments engaged in various forms of denial, obfuscation and attempts to obstruct investigation and avoid accountability. The net effect of their responses has been to deny the victims redress, through adequate judicial processes, and to deny the public adequate state accountability. These responses are not simply aimed at shielding from prosecution the perpetrators and those who have oversight of them, nor preventing political embarrassment. The various forms of denial and obstruction are also designed to ensure that collusion can continue uninterrupted. A core concern of intelligence officials and ministers has been to prevent any process that would lead to a comprehensive prohibition on involvement in operations where torture and cruel, inhuman and degrading treatment are a real possibility. The door remains wide open, and deliberately so, for British involvement in torture.




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Power and diplomacy in the post-liberal cyberspace

7 May 2020 , Volume 96, Number 3

André Barrinha and Thomas Renard

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




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The Rise of the Far Right Across Europe




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Identity, Outreach and Community: Arabic Music in the Diaspora




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Keeping the Peace: The New Landscape for European Security and Defence




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Computer Hacking: How Big is the Security Threat?




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Undercurrents: Episode 8 - Ronan Farrow on Diplomacy




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Undercurrents: Episode 9 - Digital Subversion in Cyberspace, and Oleg Sentsov's Hunger Strike




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Unfulfilled Ambitions: the State of Democracy in Africa




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Drugs and Organized Crime: The Challenges Facing Southeast Asia




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Undercurrents: Episode 11 - New Approaches to Peacebuilding, and Gender-Inclusive Growth at the G20




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Unelected Power: Finding Legitimacy in Central Banking and the Regulatory State




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A Decade on from the Financial Crisis: the Legacy and Lessons of 2008 - The Rt Hon Lord Darling of Roulanish




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Cyber Security Series: Comparing Best Practice Across Europe




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Managing the Real and Perceived Challenges Facing the World




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The Future of Democracy in Asia




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Securing Peace in the 21st Century: The Roles of Diplomacy and Statesmanship




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Assessing the Midterm Elections and the Impact on the Trump Presidency