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Specificity and affinity of the N-terminal residues in staphylocoagulase in binding to prothrombin [Computational Biology]

In Staphylococcus aureus–caused endocarditis, the pathogen secretes staphylocoagulase (SC), thereby activating human prothrombin (ProT) and evading immune clearance. A previous structural comparison of the SC(1–325) fragment bound to thrombin and its inactive precursor prethrombin 2 has indicated that SC activates ProT by inserting its N-terminal dipeptide Ile1-Val2 into the ProT Ile16 pocket, forming a salt bridge with ProT's Asp194, thereby stabilizing the active conformation. We hypothesized that these N-terminal SC residues modulate ProT binding and activation. Here, we generated labeled SC(1–246) as a probe for competitively defining the affinities of N-terminal SC(1–246) variants preselected by modeling. Using ProT(R155Q,R271Q,R284Q) (ProTQQQ), a variant refractory to prothrombinase- or thrombin-mediated cleavage, we observed variant affinities between ∼1 and 650 nm and activation potencies ranging from 1.8-fold that of WT SC(1–246) to complete loss of function. Substrate binding to ProTQQQ caused allosteric tightening of the affinity of most SC(1–246) variants, consistent with zymogen activation through occupation of the specificity pocket. Conservative changes at positions 1 and 2 were well-tolerated, with Val1-Val2, Ile1-Ala2, and Leu1-Val2 variants exhibiting ProTQQQ affinity and activation potency comparable with WT SC(1–246). Weaker binding variants typically had reduced activation rates, although at near-saturating ProTQQQ levels, several variants exhibited limiting rates similar to or higher than that of WT SC(1–246). The Ile16 pocket in ProTQQQ appears to favor nonpolar, nonaromatic residues at SC positions 1 and 2. Our results suggest that SC variants other than WT Ile1-Val2-Thr3 might emerge with similar ProT-activating efficiency.




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Processivity of dextransucrases synthesizing very-high-molar-mass dextran is mediated by sugar-binding pockets in domain V [Glycobiology and Extracellular Matrices]

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.




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Quantification of the affinities of CRISPR-Cas9 nucleases for cognate protospacer adȷacent motif (PAM) sequences [Molecular Biophysics]

The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency.




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Roles of active-site residues in catalysis, substrate binding, cooperativity, and the reaction mechanism of the quinoprotein glycine oxidase [Enzymology]

The quinoprotein glycine oxidase from the marine bacterium Pseudoalteromonas luteoviolacea (PlGoxA) uses a protein-derived cysteine tryptophylquinone (CTQ) cofactor to catalyze conversion of glycine to glyoxylate and ammonia. This homotetrameric enzyme exhibits strong cooperativity toward glycine binding. It is a good model for studying enzyme kinetics and cooperativity, specifically for being able to separate those aspects of protein function through directed mutagenesis. Variant proteins were generated with mutations in four active-site residues, Phe-316, His-583, Tyr-766, and His-767. Structures for glycine-soaked crystals were obtained for each. Different mutations had differential effects on kcat and K0.5 for catalysis, K0.5 for substrate binding, and the Hill coefficients describing the steady-state kinetics or substrate binding. Phe-316 and Tyr-766 variants retained catalytic activity, albeit with altered kinetics and cooperativity. Substitutions of His-583 revealed that it is essential for glycine binding, and the structure of H583C PlGoxA had no active-site glycine present in glycine-soaked crystals. The structure of H767A PlGoxA revealed a previously undetected reaction intermediate, a carbinolamine product-reduced CTQ adduct, and exhibited only negligible activity. The results of these experiments, as well as those with the native enzyme and previous variants, enabled construction of a detailed mechanism for the reductive half-reaction of glycine oxidation. This proposed mechanism includes three discrete reaction intermediates that are covalently bound to CTQ during the reaction, two of which have now been structurally characterized by X-ray crystallography.




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The institutionalization of the Indo-Pacific: problems and prospects

8 January 2020 , Volume 96, Number 1

Kai He and Huiyun Feng

Although the term ‘Indo-Pacific’ has become popular in the foreign policy discourse of some countries, we have yet to see any significant institution-building in the Indo-Pacific region. Borrowing insights from functional institutionalism and political leadership studies of international regimes, we introduce a ‘leadership–institution’ model to explore the problems and prospects of institutionalizing the Indo-Pacific. Through a comparative case study of the institutionalization of the Asia–Pacific vs the Indo-Pacific, we argue that two crucial factors contributed to the slow institutionalization of the Indo-Pacific as a regional system in world politics: the lack of ideational leadership from an epistemic community and the weak executive leadership from a powerful state. While ideational leaders can help states identify and expand common interests in cooperation, executive leadership will facilitate states to overcome operational obstacles in cooperation, such as the ‘collective action’ problem and the ‘relative gains’ concern. The future of institution-building in the Indo-Pacific will depend on whether and how these two leadership roles are played by scholars and states in the region. In the conclusion, we discuss the challenges of institutionalizing the Indo-Pacific and highlight China as a wild card in the future of Indo-Pacific regionalism.




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The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace

Invitation Only Research Event

12 May 2020 - 10:00am to 11:30am
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Smart Peace brings together global expertise in conflict analysis and research, peacebuilding and mediation programming, and behavioural science and evaluation. Together, Smart Peace partners are developing integrated and adaptive peace initiatives, working with local partners to prevent and resolve complex and intractable conflicts in Central African Republic, Myanmar and northern Nigeria.
 
This roundtable is an opportunity for Smart Peace partners to share the Smart Peace concept, approach and objectives, and experiences of the first phases of programme implementation. Roundtable discussions among participants from policy, practice and research communities will inform future priorities and planning for Smart Peace learning, advocacy and communication.
 
Smart Peace partners include Conciliation Resources, Behavioural Insights Team, The Centre for Humanitarian Dialogue, Chatham House, ETH Zurich, International Crisis Group and The Asia Foundation.

Nilza Amaral

Project Manager, International Security Programme




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Global aid and faith actors: the case for an actor-orientated approach to the ‘turn to religion’

4 March 2020 , Volume 96, Number 2

Emma Tomalin

In this article, drawing on the work of the development sociologist Norman Long, I make the case for an actor-oriented approach to understanding the ‘turn to religion’ by global aid actors over the past couple of decades. I ask, is the ‘turn to religion’ evidence of the emergence of post-secular partnerships or are faith actors being instrumentalized to serve neo-liberal development goals? I argue that neither option captures the whole story and advocate that the study of religion and development needs to move beyond a binary between the ‘turn to religion’ as either evidence of post-secular partnerships or of the ‘instrumentalization’ of religion by the secular global aid business, and instead to think about how faith actors themselves encounter and shape development discourses and frameworks, translate them into relevant formats and strategically employ them. Alongside the adoption of an actor-orientated approach, I build on the work of Lewis and Mosse, Olivier de Sardan and Bierschenk to view international faith-based organizations (IFBOs) as development brokers and translators. This approach allows me to articulate the distinctive role that many members of IFBOs report they play as intermediaries who shift register between the secular development language and the faith-inspired language of their local faith partners. I take the engagement of faith actors with the new Sustainable Development Goals framework as a case-study to explore this.




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20 Years Promoting Women in Peace and Security

6 March 2020

Gitika Bhardwaj

Editor, Communications & Publishing, Chatham House

Dr Joan Johnson-Freese

Professor and Charles F. Bolden Jr. Chair in Science, Space & Technology, US Naval War College
In a series exploring women in international affairs, Dr Joan Johnson-Freese speaks to Gitika Bhardwaj about the women in peace and security agenda, 20 years since its adoption, and how far women’s inclusion in space security is being considered, 50 years since women helped men take their first steps on the moon.

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The UN's first all-female peacekeeping force of more than 100 Indian women stand in Monrovia, Liberia. Photo: Getty Images.

This year marks the 20th anniversary of the adoption of UN Security Council Resolution 1325 on women, peace and security – the first to recognize the important role of women in peacebuilding. How did the resolution come into being and how significant was its adoption in 2000?  

Well it has quite an amazing history that goes back to other UN resolutions, such as the International Covenant on Civil and Political Rights and the International Covenant on Economic and Social Rights, which were passed in the 1960s and came into force in the 1970s. These were some of the biggest covenants on human and civil rights at the time but it was only later that people realised, that those who passed them, did not assume that they applied to women.

There was an attempt, subsequently, to pass the UN Convention on the Elimination of All Forms of Discrimination Against Women – commonly called the CEDAW Convention – which was widely adopted in 1979, when 187 out of 194 UN members signed, although the United States was not one of them, and in fact, the US has still not ratified the treaty. But the understanding that women’s rights were not necessarily assumed in human and civil rights action was beginning to gain recognition.

Then, in 1995, Hillary Clinton spoke in Beijing and really put it forward that women’s rights were human rights and also civil rights and we all have to address them as such. So, ‘95 really brought together all the different social groups – women’s groups, human’s rights groups, civil rights groups, and more, who pushed for the women, peace and security agenda to be passed in 2000 at the United Nations. 

The resolution on women, peace and security was a significant moment because it recognized gender equality issues were national security issues – not just social justice issues – and was soon followed by a number of other resolutions which make up the women, peace and security agenda today. 

Conflict has a disproportionate effect on women and girls, with global security threats, such as climate change,  reported to impact women more than men. In light of this, growing numbers of women are now serving on the frontlines of conflicts, in comparison to 1957-1989, when  only 20 women served as UN peacekeepers. In your view, what have been the successes of the women, peace and security agenda so far?

I think some of the successes specific to peacekeeping have been, as you mentioned, that women are increasingly part of peacekeeping forces being deployed to conflict and post-conflict situations.

Importantly, the nature of war is changing – we are no longer primarily engaged in interstate work in some places – it’s mostly intrastate work where there are often ethnic or religious overtones.

In this landscape, women are often caught up in the battle lines. They often become the heads of their households when the men are gone or injured or killed. There have also been instances of rape being used as a weapon of war and other forms of sexual violence being committed in conflict and post-conflict situations even by peacekeepers.

So, having more women as peacekeepers is important because, number one, when women see women peacekeepers, they are much less likely to fear them, and therefore, feel less threatened speaking to them. Number two, women are a less threatening presence so civil society begins to build again. Number three, women peacekeepers give women in the local area a role model of strength showing them that they can play an active role in their own security. Finally, I would say that women peacekeepers are all impressively trained to guard those under their protection.

What other successes have there been more broadly outside of peacekeeping? Well, I think one that is often cited is that there’s a 20 per cent increase in the probability of a peace agreement lasting at least two years and a 35 per cent increase in the probability of that peace agreement lasting 15 years if women are at the negotiating table. The reason being that women bring things to the table – for example focussing on the root causes of conflict – that men neglect either because they’re not aware of them or it’s not considered an issue of importance to them. 

We have a pretty abysmal history of peace agreements holding so including more women in peace negotiations, given these increases in the probability of agreements holding, seems to me the only logical thing to do.

You mentioned the inclusion of women in peace processes increases the likelihood of agreements succeeding, however, women continue to be underrepresented, comprising under 10 per cent of peace negotiators and under 4 per cent of signatories to peace agreements. Do you think there are any shortcomings with focusing on increasing the presence of women over the positions they hold and how their positions are used to further gender equality?  

I think there are a couple of aspects to this. Importantly, women have been extremely effective in leadership positions, for example, in Liberia. But it is true having women at the table does not necessarily further gender equality in the long-term and I think this was the case in Northern Ireland where the women who were at the table did not include provisions for women. But, I think, we’ve learned since then.

The most important case to cite right now, in my view, is that of women in Afghanistan. They came out of their homes, they went to school, they identified themselves as proponents of gender equality, yet now, with the US-Taliban deal, there were almost no women at the table and not a single provision in the peace agreement that deals with women. So what’s going to happen to all of these women?

Since 2000, the number of agreements referring to women has grown to 28 per cent – more than double the number between 1990-2000. However, some critics have pointed to the gap between theory and practice since many peace agreements still omit a gender perspective on peacekeeping operations. What, in your opinion, have been the failings of realising the women, peace and security agenda so far?

You know, it’s not just critics who point this out, it’s advocates as well, that there is a big gap between rhetoric and implementation. I think the reason for this, in most cases, is political will. It’s the idea that gender equality is an optional luxury – we’ll get to it when we can – and that we have more important issues to work out. Well the agency of 50 per cent of the population should not be seen as an optional luxury.

In all cases, however, it’s a question of power. There are only so many seats at the table where power is doled out and nobody wants to give up theirs to let somebody else sit down. So, I think, there is active resistance to implementing gender equality in the peace and security arena because it would mean sharing power. 

There are also some other reasons. The first is something we call the ‘blind fish’ – people who are simply unaware of gender equality issues – the second, which is interestingly by adamant supporters of the women in peace and security agenda, and that’s they are not given the budget and the authority to carry out the agenda as it should be.

A female Italian soldier from the United Nations Interim Force in Lebanon (UNIFIL) talks with a Lebanese woman in Tibnine, south Lebanon. Photo: Getty Images.

The concept of a feminist foreign policy, which places gender equality and women’s rights at the centre of its foreign policy goals, has been gaining momentum globally. Sweden became the first country in the world to adopt a feminist foreign policy in 2015, and since then, 82 countries have adopted national action plans to raise the role of women in peace processes. How effective have these measures been to furthering women in peace and security? 

That, I think, is one of the issues that women in peace and security advocates, such as myself, are currently looking at because the word ‘feminist’, for better or for worse, is a trigger in many countries.

In many countries, it’s a negative trigger, which is kind of ironic because, if you ask people, ‘Do you believe in gender equality?’, a lot of people will say, ‘Yes absolutely.’  But if you ask people, ‘Are you a feminist?’, a lot of people will say, ‘No not me.’ 

So, the question is, do we aim for a broad goal like a feminist foreign policy which would look at defining peace as, not just the absence of war, but a lot more then than that, such as creating the conditions needed for gender equality and aiming for peace and stability among other broader goals.

Or do we aim to work on a more incremental basis by trying to get more women into peacekeeping, trying to get more women into leadership positions, trying to move gender equality up the agenda as the more effective path forward?

I think the answer to the question is that it depends. If you’re Sweden, Canada or Mexico, a feminist foreign policy might be acceptable. But, if you’re the United States, it’s nowhere near acceptable. Even getting the US Defence Department to take the incremental steps of the women, peace and security agenda has been challenging.

Why do you think that is the case in the United States?

I think a lot of it has to do with power as I mentioned earlier. It has to do with an assumption that women aren’t assertive and don’t see security under the same lens as men, which is true, but which is why they are needed in this space.

I think it also, again, goes back to the point that some see it as an optional luxury rather than an absolute necessity and everybody is too busy – or simply unwilling – to change the status quo.

You mentioned the cases of Liberia and Northern Ireland, but another example that struck me was Rwanda, where women make up 62 per cent of the national legislature, far more proportionally than any other country, following provisions included in its constitution in the aftermath of the genocide of 1994.

Though equal representation between men and women is still far off for most of the world, what does the case of Rwanda and other post-conflict countries demonstrate about how to go about including more women in peacebuilding?

Well, I think the number one way to get more women into political leadership roles, where the women, peace and security agenda could then be implemented, is quotas. 

Many countries use quotas to increase more women in political participation, which Rwanda certainly does, although there are different types. There are quotas that say each political party must have X number of women as candidates and then there are quotas that say the overall number of women in the parliament must reach a certain level. 

So there are different varieties of quotas but they are all used as, kind of, affirmative action methods to at least temporarily bring the numbers up to where women’s voices are inclusive not token. 

Research has shown that until you have at least 33 per cent of a minority in an overall group – so if it’s all men then 33 per cent of this group as women – then you won’t see any change because having one or two will likely be drowned out. But, at about 33 per cent, they’re able to have political power which then means their views and their agendas are seriously considered. So, in Rwanda, that has certainly been the case and that’s been one of the big lessons learned. 

As I mentioned earlier, in Northern Ireland, the lesson learned was that it’s not enough to just have women in on peace agreements. There need to be implementation assurances written into the peace agreement that says it must be taken forward. So, in this vein, women have been learning over the years how to make a difference in male-dominated spaces. 

50 years ago, humans landed on the moon, becoming one of the most significant moments in human history. The stories of women, from Margaret Hamilton, to Katherine Johnson, to JoAnn Morgan, who all helped men take their first steps on the moon at the height of the space race, have since come into the spotlight. How will the inclusion of women need to be considered more in space security as it becomes increasingly important in international relations?

Right now, space security is at a very critical point. We have moved from a situation where there was both co-operation and competition during the space race to a situation of great power competition in space where the United States, China and Russia are, for the first time, overtly weaponizing space. When I say overtly, much of space technology is dual-use, meaning it could be used as a weapon or it could be used as something for non-military purposes.

In the past, the United States and other countries have been very careful, kind of, not to cross the Rubicon into the overt weaponization of space but that’s now ending which I think puts us in a very precarious situation. 

What seems to be missing from considerations of space security at the moment is the most threatening issue – space debris – which can only be dealt with on a multinational basis meaning it inherently requires co-operation. 

So, what I think more women in space security positions would bring, would be that inclusion and the insistence on inclusion as a pillar of space diplomacy.

If there was just a fraction of the money, and manpower, spent on space diplomacy as there is on planning for space warfare, I think we’d all be a lot better off.

NASA engineer, JoAnn Morgan, watches the blast off of Apollo 11 at the Kennedy Space Center on 16 July 1969. She was at the time NASA's only female engineer. Photo: NASA via Getty Images.

How far do current discussions about women in peace and security factor in space security?

Not at all.

Do you see the role of women in space security progressing in the future in spite of this and also despite what some have described as a broader backlash against women around the world whether in the political or in the security space?

I think there have been events over the past five or so years that have made women around the world, if anything, more acutely insistent on their participation than ever before.

We saw the marches in 2017, in the United States and worldwide, in response to what women felt was a rise in authoritarian and misogynistic governments and we have seen the rollbacks in gender equality rights in areas like reproduction too but I don’t think they’re going to take it lying down. The backlash, if anything, is going to spur women to be more, not less, active in all spaces. 

Some have argued for the need of a men, peace and security agenda, to compliment the work on women, with proponents arguing that men are needed to realise gender equality worldwide. How far are men needed as allies to realise the women, peace and security agenda? 

Well, I think, though the women, peace and security agenda has women in the title, it argues for gendered perspectives, that policies affect men and women differently. So, I think it is very important that it not be seen as dealing only with women’s issues – it deals with gendered perspectives. 

In that regard, it is very much needed to have a broadening of all of those involved. I mentioned earlier it was all women’s groups that got the women, peace and security agenda passed and now we need to include men. In fact, I would point out, NATO is a great example of an organization that has recognized the importance of looking at how policies affect men and women, girls and boys. 

So bringing more men in to support gendered perspectives is absolutely essential and looking at gendered perspectives in things like leadership roles is critical as well as gendered perspectives in everything from space policy to nuclear policy to human security issues too.

In your view, what are the greatest challenges to the uptake of gendered perspectives across the board and what, if anything, needs to change in order to realise the goals set out by the UNSC 20 years ago?

On a macro level, we need accountability. We have lots of policies, laws, national action plans and strategies of all kinds but we need accountability.

In the United States, in particular, I very much hope that accountability comes from Congress. In 2017, Congress passed the Women, Peace and Security Act on a bipartisan basis but I think it’s now up to Congress to hold organizations responsible for its implementation. 

On an organizational level, we need to get, as you said, more men involved. But, interestingly, not all women agree, so we need to have more talks among women too, be they liberal, conservative, working, non-working, mothers, not mothers etc. We may have different views but where we’re trying to go is the same and we need to work together better. 

I think among the advocates of women, peace and security, there are still issues that are up for debate like do we go for big feminist foreign policies or do we go for incremental change? In addition, are there lynchpin issues such as reproductive rights, women’s healthcare, gender equality or budget? 

You know, in the United States, I wrote in an article that although the US Defence Department gave $4 million for women, peace and security in 2018, which they were patting themselves on the back for, the Military Times pointed out that they are spending $84 million a year on Viagra.

But this is not just in the United States. 140 countries stood up at the UN to advocate for women, peace and security in 2000 but only 25 per cent of those have national action plans and any budget connected to those plans. Everyone everywhere needs to put their money where their mouths are if we are to realise the goals set out by the UNSC 20 years ago.




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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.

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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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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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Webinar: Weekly COVID-19 Pandemic Briefing – The Swedish Approach

Members Event Webinar

29 April 2020 - 10:00am to 11:00am

Online

Event participants

Professor Johan Giesecke, MD, PhD, Professor Emeritus of Infectious Disease Epidemiology, Karolinska Institute Medical University, Stockholm; State Epidemiologist, Sweden (1995-05)
Professor David Heymann CBE, Distinguished Fellow, Global Health Programme, Chatham House; Executive Director, Communicable Diseases Cluster, World Health Organization (1998-03)
Chair: Emma Ross, Senior Consulting Fellow, Global Health Programme, Chatham House

The coronavirus pandemic continues to claim lives around the world. As countries grapple with how best to tackle the virus, and the reverberations the pandemic is sending through their societies and economies, scientific understanding of how the COVID-19 virus is behaving and what measures might best combat it continues to advance.

Join us for the sixth in a weekly series of interactive webinars on the coronavirus with Professor David Heymann and special guest, Johan Giesecke, helping us to understand the facts and make sense of the latest developments in the global crisis. What strategy has Sweden embraced and why? Can a herd immunity strategy work in the fight against COVID-19? How insightful is it to compare different nations’ approaches and what does the degree of variation reveal?

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 Giesecke is professor emeritus of Infectious Disease Epidemiology at the Karolinska Institute Medical University in Stockholm. He was state epidemiologist for Sweden from 1995 to 2005 and the first chief scientist of the European Centre for Disease Prevention and Control (ECDC) from 2005 to 2014.




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Meeting the Promise of the 2010 Constitution: Devolution, Gender and Equality in Kenya

Research Event

12 May 2020 - 1:00pm to 2:00pm
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Natasha Kimani, Academy Associate, Chatham House; Head of Partnerships and Programmes, Shujaaz Inc.
Chair: Tighisti Amare, Assistant Director, Africa Programme, Chatham House
While gender equality was enshrined in Kenyan law under the 2010 constitution, gender-based marginalization remains a significant issue across all levels of society. The advent of devolution in 2013 raised hopes of enhanced gender awareness in policymaking and budgeting, with the 47 newly instituted county governments expected to tackle the dynamics of inequality close to home, but implementation has so far failed to match this initial promise. As Kenya approaches the tenth anniversary of the constitution, and with the COVID-19 pandemic throwing the challenges of gender inequality into sharper relief, it is critical to ensure that constitutional pathways are followed with the requisite level of urgency, commitment and investment to address entrenched gender issues.
 
This event, which will launch the report, Meeting the Promise of the 2010 Constitution: Devolution, Gender and Equality in Kenya, will assess the current status of efforts to devolve and adopt gender-responsive budgeting and decision-making in Kenya, and the priorities and potential future avenues to tackle the implementation gap.
 
This event will be held on the record.

To express your interest in attending, please follow this link. You will receive a Zoom confirmation email should your registration be successful.

Hanna Desta

Programme Assistant, Africa Programme




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A new profile of Steve Biko, father of Black Consciousness

9 December 2013 , Volume 69, Number 11

Xolela Mangcu Biko: A Life (IB Taurus, £12.99)

Benjamin Pogrund,

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Biko's significance stretches far beyond the brutality of his death. Photo: Mark Peters/Getty




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Year Two of the Abe Administration: Prospects for the Future of Japanese Foreign Policy and UK-Japan Relations

Research Event

11 February 2014 - 3:00pm to 5:00pm

Chatham House, London

Event participants

Kiichi Fujiwara, Professor of International Politics, Graduate School for Law and Politics, Tokyo University
Yuichi Hosoya, Professor of International Politics, Faculty of Law, Keio University
Akiko Yamanaka, Senior Visiting Research Fellow, Churchill College, University of Cambridge; Vice Minister for Foreign Affairs of Japan (2005-2006)
Chair: John Swenson-Wright, Senior Consulting Fellow, Asia Programme, Chatham House 

As Prime Minster Abe enters his second year in office, the speakers will consider future prospects for Japanese foreign policy and UK-Japan relations. 

This event is funded by the Nippon Foundation. It is held in partnership with the Nippon Foundation and the Great Britain Sasakawa Foundation.

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

Department/project




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Alain de Botton on how the news should aim to improve our lives

6 February 2014 , Volume 70, Number 1

The author of books on love, religion and Proust, explains why the news agenda should be more positive

Agnes Frimston

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Photo: Getty Images

Is the news our society’s religion today?

In the developed economies, the news now occupies a position of power at least equal to that formerly enjoyed by the faiths. Matins has been transubstantiated into the breakfast bulletin, vespers into the evening report. It also demands that we approach it with some of the same deferential expectations we would once have harboured for the faiths. Here, too, we hope to receive revelations, learn who is good and bad, fathom suffering and understand the unfolding logic of existence. And here too, if we refuse to take part in the rituals, there could be imputations of heresy.

What would you like the news to be?

It feels like there is always an infinite amount of news, so much is happening in the world every day. Yet after a while it becomes clear that the same kinds of event are recurring again and again. The details change, but all circle round the same archetypal story. Men in highly responsible positions are coming unstuck because their desires lead them to do things that, when made public, are shameful.

Identifying the underlying theme is more important in the long run than going through the details of every case. The news that matters is not so much that this MP or banker did what they did. What we need to address is why such things happen.

How do you keep the public interested in the news that does matter?

We cannot be collectively dragged into being more responsible through guilt. The Arctic ice is melting and this is going to have major, lasting implications for sea levels and weather around the world. A few people care a lot but, strangely, Taylor Swift’s legs are far more captivating. The starting point has to be indulgence towards the way our minds work. We are interested in Swift’s legs not because we are evil – but because we are wired in unhelpful ways. If we are going to be interested en masse in the defrosting poles, we need to take our fragilities on board and therefore get serious about trying to make important news not just ‘important’, but also beguiling. Then things stand a chance of changing.

You argue that we should set aside ‘neutral reporting’. Are you asking for more bias?

Many people imagine that what makes news organizations serious is their ability to provide us with information that is ‘unbiased’. But facts can only become meaningful and relevant to us when they slot into some picture of important or trivial, right or wrong. News organizations that vaunt their neutrality forget that neutrality is simply impossible. There is no risk-free, all-knowing sober set of answers to cling to. At heart, the word ‘bias’ simply alludes to the business of having a ‘take’ on existence. One may have a better or worse take, but one can’t make any sense of the flotsam of daily events in the news without having one. All of the figures we revere in history have been highly biased: each of them had a strong sense of what mattered and why, and their judgments were anything but perfectly balanced. They were just flavoured in the right way. We don’t need news stripped of bias, we need news presented to us with the best kinds of bias.

What is the purpose of foreign reporting?

Foreign reporting implicitly defers to the priorities of the state and of business, occupying itself almost exclusively with whom and where we should fight, trade or sympathize. But it should instead offer us a means by which to humanize the Other who instinctively repels, bores or frightens us and with whom we can’t, without help, imagine having anything in common.

Foreign countries also furnish a scale against which our own nation and ways of living can be assessed; they may help us to see our national oddities, blind spots and strengths. Stories from them may lead us to a fresh appreciation of the imperfect freedoms and comparative abundance of our homelands, which otherwise would be treated only as matters for grumbling or blame. Alternatively, problems with which we are all too familiar may be revealed to have been solved better elsewhere.

You mention the importance of historical perspective in reporting, so that we can respond to issues with context.

Contrary to what the news usually suggests, hardly anything is ever totally new, few things are truly amazing and very little is absolutely terrible. The economic indices are grim, but we have weathered comparable drops many times over the past century and even the worst scenarios only predict that we will return to a standard of living we had a few decades ago. A bad avian flu may disrupt international travel and defeat known drugs for a while, but research will eventually understand and contain it. The floods look dramatic, but in the end, they will affect merely a fraction of the population and recede soon.

How can photography change the way we report news?

There are now more images than ever before in the coverage we consume, but the problem lies in the lack of ambition behind their production and display. We might usefully divide news photographs into two genres. The first are images of corroboration, which do little other than confirm something we have learnt about a person or an event through an accompanying article. The second is a rarer kind of image, the photograph of revelation, whose ambition is not simply to back up what the text tells us but to advance our level of knowledge to a new point. It sets out to challenge cliché. We have lost any sense of photography’s potential as an information-bearing medium, as a force to properly introduce us to a planet that we keep conceitedly assuming that we know rather well already.

Do you feel oppressed by the news?

The pressure of not missing out makes one feel one has to care about a given topic, even when one doesn’t want to. Take Mandela’s funeral. One was supposed to care a lot, and yet, you don’t. You know the reasons why it is important, but they don’t grip you because you are focused elsewhere on subjects that, while tiny in the grand scheme of things, matter a lot within your context. It would be dangerous if hardly anyone paid attention to what the Government was doing, or what was happening to the environment. But it is not right to go from this to the demand that everyone should be interested in every item whenever the news machine calls. We badly need people whose attention is not caught up in the trends of the moment and who are not looking in the same direction as everyone else. We need people scanning the less familiar parts of the horizon.

Do you think we get the news we deserve?

Much of what we now take for granted as news has its origins in the information needed by those people taking major decisions or who are at the centre of national affairs. Ease of communication and a generous democratic impulse means that selections from the knowledge base, originally designed for decision-makers, now gets routinely sent via the media to very large numbers of people. It is as if a dossier which might properly arrive upon the desk of a Minister has accidentally been delivered to the wrong address and ends up on the breakfast table of an electrician in Pitlochry. Every day the news gives us stuff that is both interesting for some people and irrelevant to you. No wonder we’re sometimes a bit bored. It’s not our fault.




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Promoting a Culture of Development and Investment: Lessons from the Post-War Era

Research Event

5 December 2014 - 1:00pm to 2:00pm

Chatham House, London

Event participants

Giovanni Farese, Assistant Professor of Economic History, European University of Rome
Chair: Dr Paola Subacchi, Research Director, International Economics, Chatham House

This event will discuss the rise of the culture of world development. It will examine the post-war reconstruction and development projects of the 1940s through to the 1960s, including those devised at Chatham House. The speaker will argue that these projects hold valuable lessons that still apply to the current economic environment. The speaker will also discuss the key role played by Eugene R Black (1898-1992), the third president of the International Bank for Reconstruction and Development (the World Bank), who was one of the main architects of post-war reconstruction and development projects and a promoter of a ‘culture of development’.

Effie Theodoridou

+44 (0)20 7314 2760




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Demography, Gender and the Problems of Japan's Economy

Research Event

25 March 2015 - 12:30pm to 1:30pm

Chatham House, London

Event participants

TJ Pempel, Jack M. Forcey Professor, Department of Political Science, University of California, Berkeley
Chair: John Swenson-Wright, Head, Asia Programme, Chatham House

The speaker will argue that Japan’s economic problems are exacerbated by the fact that its social and employment policies favour age over youth, and men over women. In order for its economy to improve, Japan will need to loosen its rigid labour laws, encourage greater mobility and improve women’s career opportunities. Until Japan begins rewarding creativity and productivity in the workplace rather than longevity, Abenomics will fail to have the desired effect.

This event is funded by the Nippon Foundation and held in partnership with them and the Great Britain Sasakawa Foundation.

Joshua Webb

+44 (0)20 7314 3678




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Why Turkey’s Disapproval of the West’s Response to the Coup Has Limited Merit

10 August 2016

Fadi Hakura

Consulting Fellow, Europe Programme
Although Turks across the political and ideological spectrum are seething at the West’s apparently lukewarm condemnation of the abortive coup on 15 July, there are valid reasons behind the response.

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A Turkish flag attached to helium balloons as people gather to protest at Konak Square, Izmir during the July 15 failed military coup attempt. Photo by Getty Images

Signs of growing anger at the restrained denunciation of Pennsylvania-based Muslim cleric Fethullah Gulen - whose followers are thought to have played a key role in the attempted coup - are being vocalised more and more, but this criticism only shows part of the true picture.

It is true that prominent liberal Turkish intellectual Soli Ozel spoke for many when he criticised EU politicians and Western media for failing to recognise the “invaluable democratic resistance shown by all political parties in a parliament bombed by war planes”, as well as demonstrating “a lack of sensitivity, empathy and solidarity that cannot be easily digested” by not sending anyone from an EU institution to offer solidarity with the Turkish parliament.

The criticism is reasonable - officials from Western governments and regional institutions such as the Council of Europe exhibited unconditional solidarity with Ukraine during its bitter feud with Russia, which leads some to believe that Muslim-majority Turkey does not apparently deserve the same treatment as its neighbours also experiencing an unlawful attempt to seize control of the state.

Moral authority at risk

It is also right that the West should have censured the coup plotters more forcefully and built upon Turkey’s fragile unity to encourage the country to pursue further democratic reform. To quote former Swedish Prime Minister and Foreign Minister Carl Bildt: “Europe risks losing its moral authority if it does not appear particularly engaged in dealing with the coup itself.”

In addition, the EU’s strong criticism of Turkey but not France, for imposing a state of emergency and for temporarily suspending the European Convention on Human Rights, undeniably, smacks of double-standards.

However, some of the criticism falls short. To begin with, the West’s tepidity can be explained (though not wholly justified) by Erdogan’s abrasive behaviour at home and towards Western and international media.

Just three days after the coup, Erdogan threatened in his characteristically defiant tone to revive the controversial construction plans that sparked the 2013 Gezi Park protests, saying: “If we want to preserve our history, we must rebuild this historic [Ottoman-era barracks] structure, [and] we will rebuild it.”

It is also fair for Turkey to be reproached for the widespread crackdown against tens of thousands of suspected Gulenists in the aftermath of the coup. Even if it is conceivable that all 1,577 university deans who were forced to resign were Gulenists, this action will also have a lasting negative impact on the reputations and career prospects of academics unconnected to Gulen.

Fervour against Gulenism

The vigilance by the West is understandable given the Turkish government’s fervour against Gulenism in the immediate post-coup period. It would make no sense for the West to attack the coup and yet, at the same time, equivocate on flagrant violations of due process and human rights. Both efforts are mutually inclusive and identifying such violations has the greatest potential to encourage policy reversals or corrective measures.

Similarly understandable is the attention on Erdogan himself. He is the most formidable and powerful figure in a hierarchical and top-down political system, able to make fateful decisions with few effective checks and balances. He single-handedly replaced Ahmet Davutoglu as prime minister with Binali Yildirim in a clear breach of the Turkish constitution.

Despite Erdogan’s tactical attempts at embracing all the opposition parties apart from the pro-Kurdish Peoples’ Democratic Party (HDP), his refusal to renounce his ambition to transform Turkey into a powerful executive presidency indicates that this fragile political unity will not last.

Only the West has the wherewithal to moderate his policies by continuing to express its friendship with Turkey, whilst not shying away from closely monitoring, scrutinising and commenting on the post-coup developments.

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Pace Your Prose — Three Thoughts on Timing

Have you ever come across a section of a book where it felt like everything happened at breakneck speed, and you could only just barely read fast enough to keep up? Or have you seen the opposite, where it’s all nice and slow and mellow, and where you’re able to really take your time and enjoy the beauty of the words?

That’s the kind of thing I’ll be musing on today. Prose and pacing. Time and reading.

Do note, this is not about how to pace your story, that’s an entirely different topic.

The Basics

Most writers will at one point or another have heard that a full stop is a signal for the reader to breathe. The shorter the sentences are, the quicker the breathing becomes, like when you’re excited. With longer sentences, the breaths grow longer, and deeper, and you calm down.

And when you write really long sentences and don’t include any commas or other forms of punctuation your reader might just run out of breath and begin to feel a little panicked.

There’s no ideal sentence length to strive for – rather the opposite.

Continue reading Pace Your Prose — Three Thoughts on Timing at Mythic Scribes.



  • Writing Craft & Technique

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Review of Campfire Pro Writing Software

This article is by L. James Rice.

Campfire Pro is a program that aims to be a comprehensive tool for worldbuilders, ranging from authors to game designers to TTRPG Gamemasters, which means it’s got many features to explore. With that in mind, it’s probably best to give a little overview of the product before delving into its details.

First off, between gaming, screenwriting, and writing in general, I’ve seen a lot of these sorts of programs over the years and been disappointed by them more often than not. Campfire’s user interface harkens back to many older programs, keeping things relatively simple, and if you’re looking flashy bells and whistles, they aren’t here. You can, however, beautify the background with a variety of themes as well as create your own. Where this program excels is in its most important aspect, functionality, while for me at least, the biggest downfall is a less than intuitive interface. This could just be my brain, results will vary, but don’t be surprised by a tiny learning curve and the occasional “good grief, did I really just do that?” This is more about little irritants than deal breakers, however, and a little tinkering tends to find answers.

Continue reading Review of Campfire Pro Writing Software at Mythic Scribes.




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Apolipoproteins of HDL can directly mediate binding to the scavenger receptor SR-BI, an HDL receptor that mediates selective lipid uptake

S Xu
Jul 1, 1997; 38:1289-1298
Articles




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Thematic review series: Lipid Posttranslational Modifications. Protein palmitoylation by a family of DHHC protein S-acyltransferases

David A. Mitchell
Jun 1, 2006; 47:1118-1127
Thematic Reviews




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Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase

Jorge H. Capdevila
Feb 1, 2000; 41:163-181
Reviews




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Procedure for determination of free and total cholesterol in micro- or nanogram amounts suitable for studies with cultured cells

W Gamble
Nov 1, 1978; 19:1068-1070
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A spectrophotometric assay for lipid peroxides in serum lipoproteins using a commercially available reagent

M el-Saadani
Apr 1, 1989; 30:627-630
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Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review

WS Harris
Jun 1, 1989; 30:785-807
Reviews




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Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3

Mohamad Navab
Sep 1, 2000; 41:1495-1508
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Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions

M. Burstein
Nov 1, 1970; 11:583-595
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Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1

Mohamad Navab
Sep 1, 2000; 41:1481-1494
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Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly

M. Mahmood Hussain
Jan 1, 2003; 44:22-32
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Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells

JL Dixon
Feb 1, 1993; 34:167-179
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High density lipoprotein metabolism

S Eisenberg
Oct 1, 1984; 25:1017-1058
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Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans

JM Dietschy
Oct 1, 1993; 34:1637-1659
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Apolipoprotein-mediated removal of cellular cholesterol and phospholipids

JF Oram
Dec 1, 1996; 37:2473-2491
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Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

Weerapan Khovidhunkit
Jul 1, 2004; 45:1169-1196
Thematic Reviews




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Identification of multiple subclasses of plasma low density lipoproteins in normal humans

Ronald M. Krauss
Jan 1, 1982; 23:97-104
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Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein

DL Brasaemle
Nov 1, 1997; 38:2249-2263
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Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis

Dawn L. Brasaemle
Dec 1, 2007; 48:2547-2559
Thematic Reviews




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Cell cholesterol efflux: integration of old and new observations provides new insights

George H. Rothblat
May 1, 1999; 40:781-796
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Plasma cholesteryl ester transfer protein

AR Tall
Aug 1, 1993; 34:1255-1274
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Quantitation of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice

RK Tangirala
Nov 1, 1995; 36:2320-2328
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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
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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
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The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function

JP Segrest
Feb 1, 1992; 33:141-166
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Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis

IJ Goldberg
Apr 1, 1996; 37:693-707
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Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI

JE Hixson
Mar 1, 1990; 31:545-548
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'The Truth is, Chile is Unequal': What's Behind Chile's Protests

18 December 2019

Dr Christopher Sabatini

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

Lyndsey Jefferson

Digital Editor, Communications and Publishing Department
As part of a series on global protests, Dr Christopher Sabatini tells Lyndsey Jefferson why Chileans are taking to the streets.

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A demonstrator waves a Chilean flag during a protest in Santiago on 21 October 2019. Photo: Getty Images.

Why are these protests happening now?

The truth is, Chile is unequal, even though it actually reduced poverty from 1989, the time of the democratic transition, until today, from 40% to 16%.

There are a number of reasons for the protests. One is the most proximate cause, which is the increase in the subway fares, but that really doesn’t explain the underlying tensions.

One of those tensions is despite reductions in poverty, social mobility remains a large problem in Chile. It remains a very elitist country with limited social mobility. So, poverty may be reduced, but the likelihood that someone in the working middle class would reach the upper middle class has always been a stretch.

The second issue is a lack of political change. The last four presidents were the same two people.

Chile’s been governed, with the exception of Piñera, basically by the same political coalition, La Concertación, which is a combination of the Christian Democratic and Socialist parties. Piñera came from the right, an outside party, but even he has remained. There has been no renewal of the political leadership which again reinforces that lack of social mobility. 

Do the protesters have any other demands or grievances? 

The demands are amorphous and that’s part of the issue – they’re going to be difficult to meet. People are expressing a genuine desire for change but what would that change mean?

Chileans don’t necessarily want to change the economic model; they simply want more mobility. That’s difficult to do and these are untested demands. 

Chileans also want political reform. What Piñera offered is to rewrite the constitution, which was created under military government in 1980. Other than some changes here and there in terms of the electoral system and reduction of military power, it has pretty much remained intact.

Will constitutional change really address these demands? It’s simply a document that may create the rules for how power is allocated and conducted, but it’s not going to dramatically remake Chilean society.

You mentioned inequality as a key driver of the protests. Can you expand a bit more on the current economic situation of ordinary Chileans?

Chile is going to grow at only around 2-3%, but it was growing at around 4-5% earlier. A lot of those funds were ploughed into social programmes that have since been reduced. 

Chile’s economy really boomed in the early 2000s because of Chinese demands of Chilean imports. But as with any sort of commodities-based economy, the jobs it provides tend to be lower wage.

As a result, despite the fact that Chile tried to diversify its economy by investing in entrepreneurship and innovation, it hasn’t grown in a way that provides jobs that many associate with upward mobility. As Chile's economy cooled, its ability to lift people out of poverty lagged as well.

Demonstrators hold placards depicting eyes – in reference to police pellets hitting demonstrators' eyes – during a protest in Santiago on 10 December 2019. Photo: Getty Images.

Two major issues for the protesters are education and pensions – can you explain why this is?

These are two issues of the economic and social model that was held up at one time as being a model for the region, the neoliberal models that are really coming under question and are in some ways at the heart of this.

One is the privatized pension system which is failing to produce the returns that retirees need to survive. The second is the education system. Chile created a voucher system where parents can shop around and send their kids to the best schools. The idea was to create competition among schools to improve.

The problem was like any market, it created a certain amount of inequality among schools. There was a problem of some schools underperforming and being relegated poorer performing students, or students being forced to go to those schools because the more successful schools were already spoken for. 

At the end of October, the government announced a series of social reforms. Will this be enough to satisfy the protesters’ demands?

Social reforms may address some of the issues of insufficient pensions or lack of quality education, but it will take a while for them to have an effect.

The second thing is, social reforms don’t address the issues of power. At the heart of this is this idea of closed economic, political and social power. That comes about through economic growth and how you break up concentrations of wealth. Social reforms aren’t going to do that, although they’ll help on the margins. 

We’re seeing horrific scenes of police violence against protesters and dozens of people have died. Has this deterred the protesters in any way? 

No, in many ways it has sort of inspired them. It has, I think, sustained the protests.

We’re not talking massive repression and tanks rolling in like Tiananmen Square. We’re talking about tear gas, rubber bullets, some injuries and deaths, and even credible reports of torture.

It’s funny you should mention this – a class I’m teaching today is about social media and protests. One of the central arguments is that successful social protests need a martyr; they need a rallying cry.

The deaths and the repression sort of help sustain that, but moreover, social media helps communicate what’s happening through videos and pictures. It really helps maintain this sense of righteousness, disdain for the government, and this idea of the need to demand change.

Where do you see this going next?

I don’t think we know. In the 60s and 70s, the political scientist Samuel Huntington argued in Political Order in Changing Societies that as economies grow, political institutions often strain to contain and channel demands. I think we’re seeing this now.

This social ferment over political, economic and social demands is uncharted water. I don’t know where this will go, but I think we’ll see a change in the constitution. We’ve already seen a fragmenting of the party system, which I think will continue. Hopefully, that will lead to new leadership that can help reflect a change in Chile itself. 




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Roles of the DOCK-D family proteins in a mouse model of neuroinflammation [Neurobiology]

The DOCK-D (dedicator of cytokinesis D) family proteins are atypical guanine nucleotide exchange factors that regulate Rho GTPase activity. The family consists of Zizimin1 (DOCK9), Zizimin2 (DOCK11), and Zizimin3 (DOCK10). Functions of the DOCK-D family proteins are presently not well-explored, and the role of the DOCK-D family in neuroinflammation is unknown. In this study, we generated three mouse lines in which DOCK9 (DOCK9−/−), DOCK10 (DOCK10−/−), or DOCK11 (DOCK11−/−) had been deleted and examined the phenotypic effects of these gene deletions in MOG35–55 peptide-induced experimental autoimmune encephalomyelitis, an animal model of the neuroinflammatory disorder multiple sclerosis. We found that all the gene knockout lines were healthy and viable. The only phenotype observed under normal conditions was a slightly smaller proportion of B cells in splenocytes in DOCK10−/− mice than in the other mouse lines. We also found that the migration ability of macrophages is impaired in DOCK10−/− and DOCK11−/− mice and that the severity of experimental autoimmune encephalomyelitis was ameliorated only in DOCK10−/− mice. No apparent phenotype was observed for DOCK9−/− mice. Further investigations indicated that lipopolysaccharide stimulation up-regulates DOCK10 expression in microglia and that microglial migration is decreased in DOCK10−/− mice. Up-regulation of C–C motif chemokine ligand 2 (CCL2) expression induced by activation of Toll-like receptor 4 or 9 signaling was reduced in DOCK10−/− astrocytes compared with WT astrocytes. Taken together, our findings suggest that DOCK10 plays a role in innate immunity and neuroinflammation and might represent a potential therapeutic target for managing multiple sclerosis.




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

29 April 2020

Dr Georges Fahmi

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

2020-04-28-covid-19-protest-movement-mena.jpg

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

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

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

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

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

Exposes economic vulnerability

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

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

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

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

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

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

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

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

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




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Meeting the Promise of the 2010 Constitution: Devolution, Gender and Equality in Kenya

Research Event

12 May 2020 - 1:00pm to 2:00pm
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Natasha Kimani, Academy Associate, Chatham House; Head of Partnerships and Programmes, Shujaaz Inc.
Chair: Tighisti Amare, Assistant Director, Africa Programme, Chatham House
While gender equality was enshrined in Kenyan law under the 2010 constitution, gender-based marginalization remains a significant issue across all levels of society. The advent of devolution in 2013 raised hopes of enhanced gender awareness in policymaking and budgeting, with the 47 newly instituted county governments expected to tackle the dynamics of inequality close to home, but implementation has so far failed to match this initial promise. As Kenya approaches the tenth anniversary of the constitution, and with the COVID-19 pandemic throwing the challenges of gender inequality into sharper relief, it is critical to ensure that constitutional pathways are followed with the requisite level of urgency, commitment and investment to address entrenched gender issues.
 
This event, which will launch the report, Meeting the Promise of the 2010 Constitution: Devolution, Gender and Equality in Kenya, will assess the current status of efforts to devolve and adopt gender-responsive budgeting and decision-making in Kenya, and the priorities and potential future avenues to tackle the implementation gap.
 
This event will be held on the record.

To express your interest in attending, please follow this link. You will receive a Zoom confirmation email should your registration be successful.

Hanna Desta

Programme Assistant, Africa Programme