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Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines [Research]

Acute myeloid leukemia (AML) is a clonal disorder arising from hematopoietic myeloid progenitors. Aberrantly activated tyrosine kinases (TK) are involved in leukemogenesis and are associated with poor treatment outcome. Kinase inhibitor (KI) treatment has shown promise in improving patient outcome in AML. However, inhibitor selection for patients is suboptimal.

In a preclinical effort to address KI selection, we analyzed a panel of 16 AML cell lines using phosphotyrosine (pY) enrichment-based, label-free phosphoproteomics. The Integrative Inferred Kinase Activity (INKA) algorithm was used to identify hyperphosphorylated, active kinases as candidates for KI treatment, and efficacy of selected KIs was tested.

Heterogeneous signaling was observed with between 241 and 2764 phosphopeptides detected per cell line. Of 4853 identified phosphopeptides with 4229 phosphosites, 4459 phosphopeptides (4430 pY) were linked to 3605 class I sites (3525 pY). INKA analysis in single cell lines successfully pinpointed driver kinases (PDGFRA, JAK2, KIT and FLT3) corresponding with activating mutations present in these cell lines. Furthermore, potential receptor tyrosine kinase (RTK) drivers, undetected by standard molecular analyses, were identified in four cell lines (FGFR1 in KG-1 and KG-1a, PDGFRA in Kasumi-3, and FLT3 in MM6). These cell lines proved highly sensitive to specific KIs. Six AML cell lines without a clear RTK driver showed evidence of MAPK1/3 activation, indicative of the presence of activating upstream RAS mutations. Importantly, FLT3 phosphorylation was demonstrated in two clinical AML samples with a FLT3 internal tandem duplication (ITD) mutation.

Our data show the potential of pY-phosphoproteomics and INKA analysis to provide insight in AML TK signaling and identify hyperactive kinases as potential targets for treatment in AML cell lines. These results warrant future investigation of clinical samples to further our understanding of TK phosphorylation in relation to clinical response in the individual patient.




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

21 April 2020

Ben Shepherd

Consulting Fellow, Africa Programme

Nina van der Mark

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

2020-04-22-Africa-COVID-Dakar

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

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

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

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

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

Complex and unknown

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

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

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

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

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

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

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

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

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

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

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








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The recalibration of Chinese assertiveness: China's responses to the Indo-Pacific challenge

8 January 2020 , Volume 96, Number 1

Feng Liu

In response to the changing geopolitical landscape in Asia, both China and the United States attempt to alter the regional order in their own favour, both in the economic and security realms. This article shows how diverging views on future arrangements are leading to strategic shifts and increasing tension between these two Great Powers. As part of its quest for Great-Power status, China has been actively pushing its regional initiatives such as the Belt and Road Initiative (BRI) and the Asian Infrastructure Investment Bank (AIIB), as well as adopting assertive security policies towards its neighbours. In contrast, in order to counter China's growing influence America's regional strategy is undergoing a subtle shift from ‘rebalancing to Asia’ to focusing on the ‘Indo-Pacific’ region. However, amid an intensifying trade war and other challenges facing the region, China has chosen to moderate its proactive foreign policy-orientation in the past few years. In particular, China has made attempts to downplay its domestic rhetoric, rebuild strategic relationship with India and Japan, and to reassure ASEAN states in the South China Sea. In response to the Indo-Pacific strategy, it would be more effective for China to articulate a more inclusive regional vision and promote an institutional framework that also accommodates a US presence in the region.




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Centralization is Hobbling China’s Response to the Coronavirus

6 February 2020

Dr Yu Jie

Senior Research Fellow on China, Asia-Pacific Programme
The sluggish early reaction by officials should not have come as a surprise.

2020-02-06-CVT.jpg

Chinese police officers wearing masks stand in front of the Tiananmen Gate on 26 January. Photo: Getty Images.

The coronavirus outbreak in China poses a tremendous test for Beijing. Beyond the immediate public health crisis, the Chinese Communist Party faces a stuttering economy, growing public anger and distrust, and a potentially heavy blow to its global reputation.

The hesitant early response to the outbreak sheds light on the way the Chinese bureaucracy approaches crises at a time when the party leadership is tightening control at almost all levels of society. At first, officials in Wuhan attempted to censor online discussions of the virus. This changed only after President Xi Jinping’s call for a much more robust approach was followed by a sudden increase in the state media coverage of the outbreak. There is no doubt that Xi’s intervention will greatly speed up the response to the crisis, which should be welcomed.

Despite China’s experience with the SARS epidemic between 2002 and 2004, the sluggish reaction by officials in Wuhan should not have come as a surprise. The tendency among bureaucrats to play down crises is deeply entrenched. And, ironically, the party leadership’s recent push for greater bureaucratic accountability and its promise of stiffer punishment for those who take a 'do little' approach have also contributed to the habit of covering up disasters.

Xi has launched an ambitious programme to reform the governance of the Communist Party and re-centralize political control. This has reinforced the tendency of officials to avoid making important decisions and instead to wait for instructions from the party leadership.

For decades, local governments have made things happen in China. But with tighter regulation of lower-level bureaucrats, civil servants across the system now seem less ready, and able, to provide their input, making ineffective and even mistaken policy more likely.

Explainer: Coronavirus - What You Need to Know

World-renowned global health expert Professor David Heymann CBE explains the key facts and work being done on the coronavirus outbreak.

Moreover, the coronavirus outbreak could not have happened at a worse time. Last year was tumultuous and saw China fighting an economic slowdown while also dealing with an increasingly hostile international environment. Now, as the authorities take steps to contain the disease, economic activity has come to a near standstill, with public transport curbed and restaurants and entertainment venues shuttered.

This contrasts with SARS, when double-digit growth in gross domestic product enabled Beijing to raise government expenditure to tackle the outbreak. Today, the Chinese economy is running into some of the most difficult challenges it has faced since the global financial crisis.

In response to the slowdown in growth, Beijing has adopted loose fiscal policy, with an emphasis on public investment. It also continues to push big banks to cut interest rates for individual borrowers and small businesses which were already suffering from the effects of the trade war with the US before the coronavirus struck.

The outbreak should give new impetus to governments, not least those that have close economic ties with China. Being a great power with ambitions for global leadership, as well as domestic reform, is not easy. Even without multi-party elections, it involves increasing, and often uncomfortable, scrutiny. As President Xi himself has put it: the road is long and the task is weighty.

This article was originally published in the Financial Times.




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Responsive websites testing




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CBD News: In response to decision IX/16 requesting the Executive Secretary to summarize information found within existing documents on the conservation and sustainable use of biodiversity relevant for Reducing Emissions from Deforestation and Forest Degra




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CBD News: Statement by the Executive Secretary Mr. Ahmed Djoghlaf on "Biodiversity challenges and responses: Towards the Nagoya Summit on Biodiversity" at the Sixteenth Environment Congress for Asia and the Pacific, 14 September 2008, Nagoya, Ja




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CBD News: Intervention du Secrétaire exécutif M. Ahmed Djoghlaf à l'occasion de la Soirée francophone de l'Organisation internationale de la francophonieau Congrès mondial de la nature, 6 octobre 2008, Barcelone, Espagne.




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CBD News: Message from the Executive Secretary, Dr. Ahmed Djoghlaf, to the International Mountain Biodiversity Conference on "Biodiversity Conservation and Management for Enhanced Ecosystem Services: Responding to the Challenges of Global Change&quo




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CBD Communiqué: First Regional Response to the Nagoya Outcomes Will Be Elaborated in the Arab Region.




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CBD News: Message de Braulio Ferreira de Souza Dias, Secrétaire exécutif de la CDB, à l'occasion du lancement du Camp de base de 1000 Jours pour la planète, Espace pour la vie, 20 Juin 2012




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CBD Press Release: 20 years after their birth, three sister Rio Conventions reaffirm their collective responsibility for sustainable development




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CBD News: The New Delhi ASEAN-India Ministerial Statement on Biodiversity: Ministers responsible for the environment and their representatives of India and ASEAN countries have agreed to enhance awareness among all stakeholders, strive towards mainstreami




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CBD News: Fiji and Ethiopia have become the 8th and 9th Parties to the CBD respectively to deposit their instruments of ratification for the Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from Their U




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CBD Press Release: Panama and Mauritius have become the 10th and 11th countries respectively to ratify the Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Bi




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CBD Press Release: Maldives responds to Hyderabad Call for Biodiversity Champions: Entire country to become UNESCO Biosphere Reserve by 2017




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CBD News: Germany and Cambodia, on 27 and 30 August 2013 respectively, became the most recent countries to ratify/accede to the Nagoya - Kuala Lumpur Supplementary Protocol on Liability and Redress to the Cartagena Protocol on Biosafety.




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CBD News: While 87% of consumers surveyed worldwide want companies to adopt sourcing policies that respect biodiversity, only 27% of the top 100 beauty and personal care companies actually mention biodiversity on their websites or in their corporate socia




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CBD News: Islands are taking action to effectively conserve biodiversity and promote sustainable livelihoods. Despite significant vulnerabilities facing islands, leaders of island countries and countries with islands have made visionary commitments at loc




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CBD News: The 2015 UEBT Biodiversity Barometer shows that an average of 69% of respondents in nine countries say they have heard of biodiversity, but additional outreach efforts are needed for the world to reach global targets on biodiversity awareness se




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CBD News: For three days in Mexico City over 65 women and men working on issues related to gender and biodiversity in Mexico came together to share experiences and provide input into the development of a gender-responsive National Biodiversity Strategy an




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CBD News: Opening with a traditional greeting from Charles Patton, a respected elder in the Mohawk Community of Kahnawa:ke, the 25th anniversary of the entry into force of the Convention on Biological Diversity (CBD) was celebrated yesterday in Montreal a




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Soldo supports COVID-19 'digital foodstamps' response

The London-headquartered fintech startup Soldo has repurposed its spend management tools for local authorities in Italy to support its COVID-19 emergency response measures




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Technologists lead crowdsourced Coronavirus Tech Handbook response

A group of technologists has led crowdsourcing efforts to create a single repository of information for specialists fighting the Coronavirus outbreak. Techworld speaks with founder Edward Saperia to hear more about how collaboration tools can help the efforts




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Correction: Mitochondrial and nuclear genomic responses to loss of LRPPRC expression. [Additions and Corrections]

VOLUME 285 (2010) PAGES 13742–13747In Fig. 1E, passage 10, the splicing of a non-adjacent lane from the same immunoblot was not marked. This error has now been corrected and does not affect the results or conclusions of this work.jbc;295/16/5533/F1F1F1Figure 1E.




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CRISPR-Cas12a has widespread off-target and dsDNA-nicking effects [DNA and Chromosomes]

Cas12a (Cpf1) is an RNA-guided endonuclease in the bacterial type V-A CRISPR-Cas anti-phage immune system that can be repurposed for genome editing. Cas12a can bind and cut dsDNA targets with high specificity in vivo, making it an ideal candidate for expanding the arsenal of enzymes used in precise genome editing. However, this reported high specificity contradicts Cas12a's natural role as an immune effector against rapidly evolving phages. Here, we employed high-throughput in vitro cleavage assays to determine and compare the native cleavage specificities and activities of three different natural Cas12a orthologs (FnCas12a, LbCas12a, and AsCas12a). Surprisingly, we observed pervasive sequence-specific nicking of randomized target libraries, with strong nicking of DNA sequences containing up to four mismatches in the Cas12a-targeted DNA-RNA hybrid sequences. We also found that these nicking and cleavage activities depend on mismatch type and position and vary with Cas12a ortholog and CRISPR RNA sequence. Our analysis further revealed robust nonspecific nicking of dsDNA when Cas12a is activated by binding to a target DNA. Together, our findings reveal that Cas12a has multiple nicking activities against dsDNA substrates and that these activities vary among different Cas12a orthologs.




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COQ11 deletion mitigates respiratory deficiency caused by mutations in the gene encoding the coenzyme Q chaperone protein Coq10 [Lipids]

Coenzyme Q (Qn) is a vital lipid component of the electron transport chain that functions in cellular energy metabolism and as a membrane antioxidant. In the yeast Saccharomyces cerevisiae, coq1–coq9 deletion mutants are respiratory-incompetent, sensitive to lipid peroxidation stress, and unable to synthesize Q6. The yeast coq10 deletion mutant is also respiratory-deficient and sensitive to lipid peroxidation, yet it continues to produce Q6 at an impaired rate. Thus, Coq10 is required for the function of Q6 in respiration and as an antioxidant and is believed to chaperone Q6 from its site of synthesis to the respiratory complexes. In several fungi, Coq10 is encoded as a fusion polypeptide with Coq11, a recently identified protein of unknown function required for efficient Q6 biosynthesis. Because “fused” proteins are often involved in similar biochemical pathways, here we examined the putative functional relationship between Coq10 and Coq11 in yeast. We used plate growth and Seahorse assays and LC-MS/MS analysis to show that COQ11 deletion rescues respiratory deficiency, sensitivity to lipid peroxidation, and decreased Q6 biosynthesis of the coq10Δ mutant. Additionally, immunoblotting indicated that yeast coq11Δ mutants accumulate increased amounts of certain Coq polypeptides and display a stabilized CoQ synthome. These effects suggest that Coq11 modulates Q6 biosynthesis and that its absence increases mitochondrial Q6 content in the coq10Δcoq11Δ double mutant. This augmented mitochondrial Q6 content counteracts the respiratory deficiency and lipid peroxidation sensitivity phenotypes of the coq10Δ mutant. This study further clarifies the intricate connection between Q6 biosynthesis, trafficking, and function in mitochondrial metabolism.




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EDB's response to Ombudsman's direct investigation report




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Timing of immune response to COVID-19 may contribute to disease severity

(Keck School of Medicine of USC) A new USC study suggests that temporarily suppressing the body's immune system during the early stages of COVID-19 could help a patient avoid severe symptoms. That's because the research shows that an interaction between the body's two main lines of defense may be causing the immune system to go into overdrive in some patients.




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Democrats’ Desperation about Tara Reade Is Growing. So Is Their Hypocrisy.

There aren’t a ton of synonyms for the word “hypocrisy.” I’ve become aware of this problem ever since I began writing about the Tara Reade–Joe Biden situation. I keep gravitating towards phrases such as “despicable hypocrisy,” or “partisan hypocrisy,” or “unconscionable hypocrisy,” but you can only go to the well so often. Really, though, I’m not sure how else to describe the actions of someone like Senator Dianne Feinstein.You might recall that it was Feinstein, the ranking member of the Judiciary Committee, who withheld Christine Blasey Ford's allegation of sexual misconduct against Supreme Court nominee Brett Kavanaugh from the Senate so that it could not be properly vetted, in a last-ditch effort to sink the nomination.Feinstein knew that Ford's credibility was brittle -- the alleged victim could not tell us where or when the attack occurred, hadn’t mentioned Kavanugh’s name to anyone for over 30 years, and offered nothing approaching a contemporaneous witness.At first, Feinstein did not want to provide Ford’s name, or a place or time of the alleged attack, or allow the accused to see any evidence against him, denying him the ability to answer the charges.Henceforth this brand of justice could be referred to as “The Joe Biden Standard,” since it’s exactly the kind of show trial the presumptive Democratic nominee promises college kids via Title IX rules.When finally asked about Reade yesterday, Feinstein responded: “And I don’t know this person at all who has made the allegations. She came out of nowhere. Where has she been all these years? He was vice president.”To put this in perspective, when Ford came forward “out of nowhere,” Feinstein said: “Victims must be able to come forward only when they are ready.”What’s changed?During the Kavanaugh hearings Feinstein noted that “sharing an experience involving sexual assault — particularly when it involves a politically connected man with influence, authority and power — is extraordinarily difficult.”Is Biden not a politically connected man with influence, authority, and power? Feinstein is now arguing the opposite: She is saying we should dismiss Reade’s allegations because she failed to come forward against a powerful man earlier.But to answer Feinstein’s question about what Reade has been “up to” the past 27 years: Well, she’s been telling people that Biden had engaged in sexual misconduct. She relayed her story to her former neighbor, her brother, her former co-worker, and at least two other friends. It is also likely that her mother called Larry King Live asking for advice for her daughter the year of the alleged attack.Yesterday a document uncovered by local journalists in California -- somehow missed by Barack Obama’s crack vetting team -- shows Reade’s ex-husband bolstering her claim in 1996 divorce proceedings: “On several occasions [Reade] related a problem that she was having at work regarding sexual harassment, in U.S. Senator Joe Biden's office.”The reaction to the divorce papers has been extraordinary. Biden defenders argue that because Reade alleged “sexual harassment” -- a catch-all term used in the 1990s when men were getting away with despicable behavior far more often -- it proves her story has changed. Biden, through his deputy campaign manager Kate Bedingfield, alleges that “more and more inconsistencies” come up every day.Even if Reade didn't tell everyone everything that allegedly happened every time she mentioned the incident, that doesn’t definitively prove anything. If it did, none of us would have ever heard the name Christine Blasey Ford.Indeed, at time of Ford’s evolving story, there was a slew of journalists taking deep dives into the unreliability of memory and trauma and complexities of relaying assault allegations. I assume that science hasn’t changed in two years.Let’s also not forget that, despite Ford’s inconsistencies, Biden still argued that Kavanaugh should be presumed guilty. Why shouldn’t he?It is also quite amazing to see Biden’s defenders implicitly contending that Reade is only credibly claiming that she was sexually harassed for nearly 30 years, so her story must be politically motivated.Even if we concede that Reade is a wily Sanders operative or Putin stooge, what political motive could Reade possibly have had back in 1993 -- after working for Biden -- to smear the senator? What motive did she have to repeat that story to her family before Sanders was a candidate or Putin was running Russia?By the way, liberals have never argued that political motivations should be disqualifying. Ford came forward, by her own admission, because she did not believe the man who had allegedly assaulted her in high school should be given a seat on highest court in the land. Reade says she doesn’t want a man who allegedly assaulted her -- when he was in his 50s -- to hold the most powerful office in the world.Feinstein, of course, isn’t the only one to engage in this kind of transparent double standard. When asked about Reade, the idealist Alexandria Ocasio-Cortez, said, “I’m not sure. Frankly, this is a messy moment, and I think we need to acknowledge that -- that it is not clear-cut.”Where was all this hand-wringing and caution over the messiness of sexual-assault claims when nearly every Democrat and all their allies in the press were spreading Julie Swetnick’s alleged “gang rape” piece? Nowhere.AOC, whose position on Biden has evolved, invited Ana Maria Archila, the women who had famously cornered a weak-kneed senator Jeff Flake in an elevator and yelled at him about Kavanaugh, to the 2019 State of the Union address. Archila now says, “I feel very trapped.”I bet.People point out that there are numerous sexual-misconduct allegations leveled at Donald Trump. Indeed. If they haven’t yet, news outlets should scrutinize and investigate the credibility of those allegations, as they did for Biden but not for Kavanaugh. But it’s important to remember that Trump accuser E. Jean Carroll was given immediate and widespread coverage on cable news, while Reade reportedly wasn’t asked to tell her story by any major network -- save Fox News -- until this week.Of course, most Biden defenders are being purposely obtuse about the debate -- Mona Charen’s recent column is an excellent example. The problem isn’t that Biden is being treated unjustly, or that he should be treated unjustly; it’s that he is being treated justly by the same people who treat others unjustly. Democrats have yet to explain why Biden is afforded every benefit of the doubt but not Kavanaugh, and not millions of college students.Public figures such as Biden have every right to demand fair hearings and due process. Voters have every right to judge the credibility of both accuser and accused. Many women are victims. Many women are victims who are powerless to prove it. And some women are frauds. You can’t keep demanding that our political system adjudicate similar incidents under two completely differ set of rules. It’s untenable.





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Despite lockdown, no letup in Chicago's murder rate

The streets of Chicago may be largely empty as residents hunker down from coronavirus but some of the city's most deprived neighborhoods are still echoing to the sound of deadly gunfire and raucous partying. While significant falls in crime have been one of the few positive side effects of lockdowns in much of the United States and elsewhere, they have barely made a dent in the homicide rate in Chicago, a city that has long recorded the most murders in the country. Chicago police say 56 murders were committed in April despite statewide stay-at-home orders -- only a fraction lower than the 61 for the same month in 2019 -- while last weekend, the first of the new month, four people were killed and 46 others shot and wounded.





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Working women, and especially single moms, are hit hard by coronavirus downturn

Now Swain, 40, spends her evenings having dinner with her girls, age 5 and 8, and studying for her real-estate license, which she hopes will provide more long-term stability for her family after the coronavirus crisis upended her livelihood. "I can't be put in a position like this again," said Swain, a bartender for 20 years. American women are taking an outsized hit from the early wave of unemployment caused by the pandemic, due to the nature of the jobs that were lost in the business shutdowns to control the spread of the coronavirus.





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Shav-A sees positives despite COVID

Up-and-coming entertainer Shav-A says the COVID-19 pandemic made her reflect on her life. "I needed a reset. With all this downtime, I have realised that I needed to stop and rethink a lot of things that are going on in my life, and it also...




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Alumni and Students From Greater China Donate PPE to NY Healthcare Workers Desperate for Gear

As the pandemic ebbed in China, alumni from the region raised more than $2.1 million to send crucial protective gear to New York healthcare workers.




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Beyond CARES: Economist Glenn Hubbard on Government Response to COVID-19

Hubbard asks: Can we design a more effective plan, in case of a next time?




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Responsible Business 2019

Conference

Priorities, practices and principles in a digital age

28 February 2019 - 9:30am to 5:00pm

Chatham House, London

Overview

Agenda

Speakers

Pricing and booking information

Sponsors

Media partners and supporting organizations

Venue and accommodation

Press registration

Contact us

Ever-increasing consumer, investor and employee awareness continues to drive the business case for responsible behaviour, and recent events have highlighted the growing need for corporate accountability and transparency from C-suite behaviour to global supply chain management. But what exactly are these expectations across different sectors, as the acceleration of the digital age continues to present new risks, opportunities and concerns? How can the right behaviours be encouraged? 

Furthermore, ongoing political transitions and regulatory stances over the last two years have shone a light on companies’ potential and realized impact on society. With trust in political institutions low, many are calling upon businesses not only to reflect their values but to actively bridge the governance gap on issues such as equality, sustainability and human rights, in their own business operations and beyond.  But what role should business be adopting, and what are the consequences of this trend? What are the perceived trade-offs? 

The past year has seen examples of technology leaders being held to account for the mishandling of data, global corporations taking a proactive stance on contentious political issues and executive behaviour directly impacting share price. It is critical that policy-makers and business leaders re-evaluate their priorities, practices and principles as technology and politics continue to reshape the landscape. 

The third annual Chatham House Responsible Business conference will explore key questions, including:

  • Who will lead the corporate responsibility agenda? What is driving responsible behaviour? 
  • To what extent has there been a policy retreat in this space? What has been the response to this, and what does it mean for different roles and responsibilities? 
  • What are the new priorities for responsible business in a digital age? How have recent events demonstrated a shift in expectations? 
  • How can policy-makers and companies foster the integration of human rights across global supply chains, international trade and regional business operations?
  • What is the role of corporate governance and leadership in setting standards and promoting responsible business? Is this a new era of corporate activism? 

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

Twitter
@CH_Events
#CHBusiness

Thursday 28 February
0920

Welcome and chair's opening remarks
Dr Robin Niblett, Director, Chatham House

Keynote address
Simon Thompson, Chairman, Rio Tinto

Questions and discussion

Session One | Leaders and Drivers
1000-1115

This opening session will examine the status of corporate leadership in responsible business, evolving policy environments and stakeholder expectations, and how they continue to shape roles and responsibilities. 

  • How are expectations for responsible business evolving? Where has this been most apparent in the past 18 months, and what is driving these shifts? 
  • Do policy and regulation continue to be effective at encouraging responsible business behaviour? Where is regulation most effective in this space? 
  • Given current political sentiments and levels of trust, what role should business play in creating a sustainable economy and a more equal society? What are the implications of this?  
  • What can business leaders learn from existing examples of corporate activism? 
  • Does a trade-off exist between responsible practices and economic competitiveness, or do commercial drivers incentivize better behaviours? How does this differ across different markets and regions?

Chair
Tamzin Booth, European Business Editor, The Economist

Speakers
Helena Morrissey, Head of Personal Investing, Legal & General Investment Management, and Founder of the 30% Club
Ioannis Ioannou, Associate Professor of Strategy and Entrepreneurship, London Business School
Phil Bloomer, Executive Director, Business & Human Rights Resource Centre​
Sue Garrard, EVP Sustainable Business and Communications, Unilever (2014-18)

Questions and discussion

1115-1145 Refreshments

Session Two | Practices and Transparency
1145-1300

This session will address regulatory frameworks and economic incentives governing responsible business conduct, as well as human rights and business operations across global supply chains. 

  • How prominent are business and human rights issues on national policy agendas? To what extent has this influenced business behaviours across different sectors and regions? 
  • What progress has been made with regards to the UN Guiding Principles for Business and Human Rights? What has most effectively driven their integration? 
  • To what extent can public opinion and public awareness help narrow the governance gap? How can investors actively promote and enforce better governance practices? 
  • Does transparency necessarily lead to accountability, and in turn increase consumer and investor trust? What are the implications of this? 
  • How can due diligence and reporting be made more efficient to enhance accountability as well as transparency across supply chains and investments? Can digital solutions be employed to achieve social and environmental best practice?

Chair
Bennett Freeman, Deputy Assistant Secretary for Democracy, Human Rights and Labor, US Department of State (1999–2001)

Speakers
Gillian Caldwell, CEO, Global Witness
Madelaine Tuininga, Head of Unit, DG Trade, European Commission
Sharan Burrow, General Secretary, International Trade Union Confederation 
Guus Houttuin, Trade Adviser, European External Action Service, and Chair, the OECD Multi-stakeholder Steering Group 

Questions and discussion

1300-1400 Lunch

Session Three | Responsibility in the Digital Age
1400-1515

This session will examine the risks and opportunities presented by digitization and other technological developments for responsible business practices. 

  • What have events over the past year indicated regarding stakeholder concerns accompanying specific technologies and business practices? How have different sectors and companies responded? 
  • What are the responsible business issues that accompany the transition to a digital-first society? What can be learned from the challenges of regulating tech titans?
  • How can businesses ensure data privacy and help customers with digital access to maintain trust and maximize benefits from digital transformation? 
  • To what extent is the proliferation of information through technology already enhancing corporate accountability and transparency? What are the risks here? 

Chair
John Thornhill, Innovation Editor, Financial Times

Speakers
Nuala O’Connor, President and CEO of the Center for Democracy and Technology
Simon McDougall, Executive Director, Technology Policy and Innovation, Information Commissioner’s Office​
Rebecca MacKinnon, Director, Ranking Digital Rights, New America
Sarah Drinkwater, Director, Tech and Society Solutions Lab, Omidyar Network

Questions and discussion

1515-1545 Afternoon refreshments

Session Four | Governance
1545-1700

This closing session will explore the role of corporate governance in setting standards and leading responsible business practices, including diversity and inclusion as well as C-suite accountability and transparency. 

  • How are businesses responding to expectations of good corporate governance and leadership in the digital age? Are businesses equipped to maintain high standards of accountability and transparency in the era of open data and social media?
  • Do business leaders have a responsibility to embody as well as promote high standards of responsible business and ethical leadership? What lessons can be learnt from corporate governance failings? 
  • What role should business leaders play in the broader political environment? Is corporate activism part of responsible governance, and what are the risks?
  • What are the best strategies to empower diversity and foster inclusion in a rapidly changing global economy? Should diversity and inclusion begin in the boardroom?

Chair
Aris Vrettos, Director of Open Programmes and International Markets, Cambridge Institute for Sustainability Leadership

Speakers
Catherine Howarth, CEO, ShareAction 
Jane Ellis, Director, GoodCorporation
Mo Ibrahim, Founder, Mo Ibrahim Foundation 
Alison Cottrell, CEO, Banking Standards Board

Questions and discussion

1700 Close of conference and drinks reception 

© The Royal Institute of International Affairs 2019

Keynote Speaker

Speakers

Phil Bloomer

Executive Director, Business & Human Rights Resource Centre

Tamzin Booth

Business Editor, The Economist

Sharan Burrow

General Secretary, International Trade Union Confederation

Gillian Caldwell

CEO, Global Witness

Alison Cottrell

CEO, Banking Standards Board

Sarah Drinkwater

Director, Tech and Society Solutions Lab, Omidyar Network

Jane Ellis

Director, GoodCorporation

Bennett Freeman

Deputy Assistant Secretary for Democracy, Human Rights and Labor, United States (1999-2001)

Sue Garrard

EVP Sustainable Business and Communications, Unilever (2014-18)

Guus Houttuin

Trade Adviser, European External Action Service, and Chair, the OECD Multi-stakeholder Steering Group

Catherine Howarth

CEO, ShareAction

Mo Ibrahim

Founder, Mo Ibrahim Foundation

Ioannis Ioannou

Associate Professor of Strategy and Entrepreneurship, London Business School

Rebecca MacKinnon

Director, Ranking Digital Rights, New America

Simon McDougall

Executive Director, Technology Policy and Innovation, Information Commissioner's Office

Dame Helena Morrissey

Head of Personal Investing, Legal & General Investment Management; Founder, 30% Club

Dr Robin Niblett CMG

Director, Chatham House

Nuala O'Connor

President and CEO, Center for Democracy & Technology

John Thornhill

Innovation Editor, Financial Times

Madelaine Tuininga

Head of Unit, DG Trade, European Commission

Aris Vrettos

Director of Open Programmes and International Markets, Cambridge Institute for Sustainability Leadership

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Department/project




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Power Politics Could Impede Progress on Responsible Regulation of Cyberspace

3 December 2019

Harriet Moynihan

Senior Research Fellow, International Law Programme
A new Chatham House paper examines the prospects of countries reaching agreement on issues of sovereignty and non-intervention in cyberspace in the face of persistent, low-level, state-to-state cyber attacks.

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

In discussions to date about how international law applies in cyberspace, commentators have tended to focus their attention on how the rules on the use of force, or the law of armed conflict, apply to cyber activities conducted by states that give rise to physical damage, injury or death.

But in practice, the vast majority of state cyberattacks fall below this threshold. Far more common are persistent, low-level attacks that may leave no physical trace but that are capable of doing significant damage to a state’s ability to control its systems, often at serious economic cost.

Such cyber incursions might include network disruptions in the operation of another government’s websites; tampering with electoral infrastructure to change or undermine the result; or using cyber means to destabilize another state’s financial sector.

For these kinds of cyber operation, the principle of sovereignty, and the principle of non-intervention in another state’s internal affairs, are the starting point.

A UN Group of Government Experts (GGE) agreed in 2013 and 2015 that the principles in the UN Charter, including sovereignty and the prohibition on intervention in another state’s affairs, apply to states’ activities in cyberspace. The 2015 GGE also recommended eleven (non-binding) norms of responsible state behaviour in cyberspace.

However, states have not yet reached agreement on how to apply these principles. Until recently, there has also been very little knowledge of what states actually do in cyberspace, as they usually conduct cyber operations covertly and have been reluctant to put their views on record.

A new Chatham House research paper analyses the application of the principles of sovereignty and non-intervention to state cyberattacks that fall below the principle of use of force. As well as analysing the application of the law in this area, the paper also makes recommendations to governments on how they might best make progress in reaching agreement in this area.

Existing rules or new rules?

As the research paper makes clear, there is currently some debate, principally between countries in the West, about the extent to which sovereignty is a legally binding rule in the context of cyberspace and, if so, how it and the principle of non-intervention might apply in practice.

In the last few years, certain states have put on record how they consider international law to apply to states’ activities in cyberspace, namely the UK, Australia, France and the Netherlands. While there may be some differences in their approaches, which are discussed in the paper, there also remains important common ground: namely, that existing international law already provides a solid framework for regulating states’ cyber activities, as it regulates every other domain of state-to-state activity.

There is also an emerging trend for states to work together when attributing cyberattacks to hostile states, enabling them to call out malign cyber activity when it violates international law. (See, for example, the joint statements made in relation to the NotPetya cyber attack and malicious cyber activity attributed to the Russian government).

However, other countries have questioned whether existing international law as it stands is capable of regulating states’ cyber interactions and have called for ‘new legal instruments’ in this area.

This includes a proposal by the Shanghai Cooperation Organization (led by Russia and China) for an International Code of Conduct on Information Security, a draft of which was submitted to the UN in 2011 and 2015, without success. The UN has also formed a new Open-Ended Working Group (OEWG) under a resolution proposed by Russia to consider how international law applies to states’ activities in cyberspace.

The resolution establishing the OEWG, which began work earlier this year, includes the possibility of the group ‘introducing changes to the rules, norms and principles of responsible behaviour of States’ agreed in the 2013 and 2015 GGE reports. In the OEWG discussions at the UN in September, several countries claimed that a new legal instrument was needed to fill the ‘legal vacuum’ (Cuba) or ‘the gap of ungoverned areas’ (Indonesia).

It would be concerning if the hard-won consensus on the application of international law to cyberspace that has been reached at past GGEs started to unravel. In contrast to 2013 and 2015, the 2017 meeting failed to reach an agreement.

On 9 December, a renewed GGE will meet in New York, but the existence of the OEWG exploring the same issues in a separate process reflects the fact that cyber norms have become an area of geopolitical rivalry.

Aside from the application of international law, states are also adopting divergent approaches to the domestic regulation of cyberspace within their own territory. The emerging trend towards a ‘splinternet’ – i.e. between states that believe the internet should be global and open on the hand, and those that favour a ‘sovereignty and control’ model on the other  – is also likely to make discussions at the GGE more challenging.

Distinct from the international law concept of sovereignty is the notion of ‘cybersovereignty’, a term coined by China to describe the wide-ranging powers it assumes under domestic law to regulate its citizens’ access to the internet and personal data within its territory. This approach is catching on (as reflected in Russia’s recently enacted ‘Sovereign Internet Law’), with other authoritarian states likely to follow suit.

The importance of non-state actors

In parallel with regional and UN discussions on how international law applies, a number of initiatives by non-state actors have also sought to establish voluntary principles about responsible state behaviour in cyberspace.

The Global Commission on the Stability of Cyberspace, a multi-stakeholder body that has proposed principles, norms and recommendations to guide responsible behaviour by all parties in cyberspace, recently published its final report. The Cybersecurity Tech Accord  aims to promote collaboration between tech companies on stability and resilience in cyberspace. President Macron’s ‘Paris Call for Trust and Security in Cyberspace’ has to date received the backing of 67 states, 139 international and civil society organizations, and 358 private-sector organizations.

It remains to be seen in the long term whether the parallel processes at the UN will work constructively together or be competitive. But notwithstanding the challenging geopolitical backdrop, the UN GGE meeting next week at the least offers states the opportunity to consolidate and build on the results of past meetings; to increase knowledge and discussion about how international law might apply; and to encourage more states to put their own views of these issues on the record.




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COQ11 deletion mitigates respiratory deficiency caused by mutations in the gene encoding the coenzyme Q chaperone protein Coq10 [Lipids]

Coenzyme Q (Qn) is a vital lipid component of the electron transport chain that functions in cellular energy metabolism and as a membrane antioxidant. In the yeast Saccharomyces cerevisiae, coq1–coq9 deletion mutants are respiratory-incompetent, sensitive to lipid peroxidation stress, and unable to synthesize Q6. The yeast coq10 deletion mutant is also respiratory-deficient and sensitive to lipid peroxidation, yet it continues to produce Q6 at an impaired rate. Thus, Coq10 is required for the function of Q6 in respiration and as an antioxidant and is believed to chaperone Q6 from its site of synthesis to the respiratory complexes. In several fungi, Coq10 is encoded as a fusion polypeptide with Coq11, a recently identified protein of unknown function required for efficient Q6 biosynthesis. Because “fused” proteins are often involved in similar biochemical pathways, here we examined the putative functional relationship between Coq10 and Coq11 in yeast. We used plate growth and Seahorse assays and LC-MS/MS analysis to show that COQ11 deletion rescues respiratory deficiency, sensitivity to lipid peroxidation, and decreased Q6 biosynthesis of the coq10Δ mutant. Additionally, immunoblotting indicated that yeast coq11Δ mutants accumulate increased amounts of certain Coq polypeptides and display a stabilized CoQ synthome. These effects suggest that Coq11 modulates Q6 biosynthesis and that its absence increases mitochondrial Q6 content in the coq10Δcoq11Δ double mutant. This augmented mitochondrial Q6 content counteracts the respiratory deficiency and lipid peroxidation sensitivity phenotypes of the coq10Δ mutant. This study further clarifies the intricate connection between Q6 biosynthesis, trafficking, and function in mitochondrial metabolism.




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Cybersecurity in the Commonwealth: Building the Foundations of Effective National Responses in the Caribbean

Invitation Only Research Event

8 March 2019 - 9:00am to 5:30pm

Bridgetown, Barbados

Event participants

Joyce Hakmeh, Cyber Research Fellow, International Security Department, Chatham House

This workshop is the second in a series in the 'Implementing the Commonwealth Cybersecurity Agenda' project. The workshop aims to provide a multi-stakeholder pan-Commonwealth platform to discuss how to take the implementation of the 'Commonwealth Cyber Declaration' forward with a focus on the second pillar of the declaration – building the foundations of an effective national cybersecurity response with eight action points. 

As such, the workshop gathers different project implementers under the UK Foreign and Commonwealth Office’s Cyber Programme, in addition to other key relevant stakeholders from the global level, to explore ongoing initiatives which aim to deliver one or more of pillar two’s action points.

The workshop addresses issues from a global perspective and a Commonwealth perspective and will include presentations from selected partners from different Commonwealth countries.

Calum Inverarity

Research Analyst and Coordinator, International Security Department
+44 (0) 207 957 5751




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Cyber Governance in the Commonwealth: Towards Stability and Responsible State Behaviour in Cyberspace

Invitation Only Research Event

7 October 2019 - 10:30am to 5:30pm

Addis Ababa, Ethiopia

This roundtable is part of a series under the project, 'Implementing the Commonwealth Cybersecurity Agenda', funded by the UK Foreign and Commonwealth Office (FCO). The roundtable aims to provide a multi-stakeholder, pan-Commonwealth platform to discuss how to implement the Commonwealth Cyber Declaration with a focus on its third pillar 'To promote stability in cyberspace through international cooperation'.

In particular, the roundtable focuses on points 3 and 4 of the third pillar which revolve around the commitment to promote frameworks for stability in cyberspace including the applicability of international law, agreed voluntary norms of responsible state behaviour and the development and implementation of confidence-building measures consistent with the 2015 report of the UNGGE. 

The workshop also focuses on the commitment to advance discussions on how existing international law, including the Charter of the United Nations and applicable international humanitarian law, applies in cyberspace.

The roundtable addresses the issue of global cyber governance from a Commonwealth perspective and will also include a discussion around the way forward, the needed capacity of the different Commonwealth countries and the cooperation between its members for better cyber governance.

Participants include UNGGE members from Commonwealth countries in addition to representatives to the UN Open-Ended Working Group from African countries as well as members from academia, civil society and industry.

Calum Inverarity

Research Analyst and Coordinator, International Security Department
+44 (0) 207 957 5751




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Human Control Is Essential to the Responsible Use of Military Neurotechnology

8 August 2019

Yasmin Afina

Research Assistant, International Security Programme
The military importance of AI-connected brain–machine interfaces is growing. Steps must be taken to ensure human control at all times over these technologies.

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A model of a human brain is displayed at an exhibition in Lisbon, Portugal. Photo: Getty Images.

Technological progress in neurotechnology and its military use is proceeding apace. As early as the 1970s, brain-machine interfaces have been the subject of study. By 2014, the UK’s Ministry of Defence was arguing that the development of artificial devices, such as artificial limbs, is ‘likely to see refinement of control to provide… new ways to connect the able-bodied to machines and computers.’ Today, brain-machine interface technology is being investigated around the world, including in Russia, China and South Korea.

Recent developments in the private sector are producing exciting new capabilities for people with disabilities and medical conditions. In early July, Elon Musk and Neuralink presented their ‘high-bandwidth’ brain-machine interface system, with small and flexible electrode threads packaged into a small device containing custom chips and to be inserted and implanted into the user’s brain for medical purposes.

In the military realm, in 2018, the United States’ Defense Advanced Research Projects Agency (DARPA) put out a call for proposals to investigate the potential of nonsurgical brain-machine interfaces to allow soldiers to ‘interact regularly and intuitively with artificially intelligent, semi-autonomous and autonomous systems in a manner currently not possible with conventional interfaces’. DARPA further highlighted the need for these interfaces to be bidirectional – where information is sent both from brain to machine (neural recording) and from machine to brain (neural stimulation) – which will eventually allow machines and humans to learn from each other.

This technology may provide soldiers and commanders with a superior level of sensory sensitivity and the ability to process a greater amount of data related to their environment at a faster pace, thus enhancing situational awareness. These capabilities will support military decision-making as well as targeting processes.

Neural recording will also enable the obtention of a tremendous amount of data from operations, including visuals, real-time thought processes and emotions. These sets of data may be used for feedback and training (including for virtual wargaming and for machine learning training), as well as for investigatory purposes. Collected data will also feed into research that may help researchers understand and predict human intent from brain signals – a tremendous advantage from a military standpoint.

Legal and ethical considerations

The flip side of these advancements is the responsibilities they will impose and the risks and vulnerabilities of the technology as well as legal and ethical considerations.

The primary risk would be for users to lose control over the technology, especially in a military context; hence a fail-safe feature is critical for humans to maintain ultimate control over decision-making. Despite the potential benefits of symbiosis between humans and AI, users must have the unconditional possibility to override these technologies should they believe it is appropriate and necessary for them to do so.

This is important given the significance of human control over targeting, as well as strategic and operational decision-making. An integrated fail-safe in brain-machine interfaces may in fact allow for a greater degree of human control over critical, time-sensitive decision-making. In other words, in the event of incoming missiles alert, while the AI may suggest a specific course of action, users must be able to decide in a timely manner whether to execute it or not.

Machines can learn from coded past experiences and decisions, but humans also use gut feelings to make life and death decisions. A gut feeling is a human characteristic that is not completely transferable, as it relies on both rational and emotional traits – and is part of the ‘second-brain’ and the gut-brain axis which is currently poorly understood. It is however risky to take decisions solely on gut feelings or solely on primary brain analysis—therefore, receiving a comprehensive set of data via an AI-connected brain-machine interface may help to verify and evaluate the information in a timely manner, and complement decision-making processes. However, these connections and interactions would have to be much better understood than the current state of knowledge. 

Fail-safe features are necessary to ensure compliance with the law, including international humanitarian law and international human rights law. As a baseline, human control must be used to 1) define areas where technology may or may not be trusted and to what extent, and 2) ensure legal, political and ethical accountability, responsibility and explainability at all times. Legal and ethical considerations must be taken into account from as early as the design and conceptualizing stage of these technologies, and oversight must be ensured across the entirety of the manufacturing supply chain.  

The second point raises the need to further explore and clarify whether existing national, regional and international legal, political and ethical frameworks are sufficient to cover the development and use of these technologies. For instance, there is value in assessing to what extent AI-connected brain-machine interfaces will affect the assessment of the mental element in war crimes and their human rights implications.

In addition, these technologies need to be highly secure and invulnerable to cyber hacks. Neural recording and neural stimulation will be directly affecting brain processes in humans and if an adversary has the ability to connect to a human brain, steps need to be taken to ensure that memory and personality could not be damaged.

Future questions

Military applications of technological progress in neurotechnology is inevitable, and their implications cannot be ignored. There is an urgent need for policymakers to understand the fast-developing neurotechnical capabilities, develop international standards and best practices – and, if necessary, new and dedicated legal instruments – to frame the use of these technologies.

Considering the opportunities that brain-machine interfaces may present in the realms of security and defence, inclusive, multi-stakeholder discussions and negotiations leading to the development of standards must include the following considerations:

  • What degree of human control would be desirable, at what stage and by whom? To what extent could human users be trusted with their own judgment in decision-making processes?
  • How could algorithmic and human biases, the cyber security and vulnerabilities of these technologies and the quality of data be factored into these discussions?
  • How can ethical and legal considerations be incorporated into the design stage of these technologies?
  • How can it be ensured that humans cannot be harmed in the process, either inadvertently or deliberately?
  • Is there a need for a dedicated international forum to discuss the military applications of neurotechnology? How could these discussions be integrated to existing international processes related to emerging military applications of technological progress, such as the Convention on Certain Conventional Weapons (CCW) Group of Governmental Experts on Lethal Autonomous Weapons Systems?




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Webinar: Idlib at Risk – Doctors and First Responders in Northwest Syria

Members Event Webinar

23 April 2020 - 5:00pm to 6:00pm

Online

Event participants

Dr Munzer al-Khalil, Head, Idlib Health Directorate
Raed Al Saleh, Director, Syria Civil Defence (The White Helmets)
Alaa Rajaa Mughrabieh, Child Protection Officer, Hurras Network
Chair: Dr Lina Khatib, Director, Middle East and North Africa Programme, Chatham House

 

In Syria, uncertainty about the safety of the ceasefire agreed between Russia and Turkey last month is inhibiting 1 million people who have been displaced since December 2019 from returning home.

The looming COVID-19 global health crisis threatens to further devastate those most vulnerable as the conditions in northwest Syria’s refugee camps make it hard to practice common social distancing guidelines. Added to this, the medical infrastructure in the region has been decimated after years of bombings which has disabled over 70 health facilities since April 2019.

This webinar highlights the potentially catastrophic risks of a coronavirus outbreak in Idlib and displacement camps in northwest Syria by speaking with medical and civil society actors working in the region. How are doctors and local humanitarian organizations scaling up their medical and prevention response to the COVID-19 outbreak?

What key supplies such as ventilators, testing kits and critical sanitary equipment are still lacking? And how can the international community step in to help mitigate the potentially devastating consequences of an outbreak in these refugee camps?

This event is run in collaboration with The Syria Campaign, a human rights organization working with Syrian civil society to raise the voices of those struggling for democracy, and support frontline activists and humanitarians.




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SUV25 and {micro}PERCIST: Precision Imaging of Response to Therapy in Co-Clinical FDG-PET Imaging of Triple Negative Breast Cancer (TNBC) Patient-Derived Tumor Xenografts (PDX)

Numerous recent works highlight the limited utility of established tumor cell lines in recapitulating the heterogeneity of tumors in patients. More realistic preclinical cancer models are thought to be provided by transplantable, patient-derived tumor xenografts (PDX). Inter- and intra-tumor heterogeneity of PDX, however, present several challenges in developing optimal quantitative pipelines to assess response to therapy. The objective of this work was to develop and optimize image metrics of FDG-PET to assess response to combination docetaxel/carboplatin therapy in a co-clinical trial involving triple negative breast cancer (TNBC) PDX. We characterize the reproducibility of SUV metrics to assess response to therapy and optimize a preclinical PERCIST (µPERCIST) paradigm to complement clinical standards. Considerations in this effort included variability in tumor growth rate and tumor size; solid tumor vs. tumor heterogeneity and necrotic phenotype; and optimal selection of tumor slice versus whole tumor. A test-retest protocol was implemented to optimize the reproducibility of FDG-PET SUV thresholds, SUVpeak metrics, and µPERCIST parameters. In assessing response to therapy, FDG-PET imaging was performed at baseline and +4 days following therapy. The reproducibility, accuracy, variability, and performance of imaging metrics to assess response to therapy were determined. We defined an index—"Quantitative Response Assessment Score (QRAS)"—to integrate parameters of prediction and precision, and thus aid in selecting optimal image metrics of response to therapy. Our data suggests that a threshold value of 25% (SUV25) of SUVmax was highly reproducible (<9% variability). Concordance and reproducibility of µPERCIST were maximized at α=0.7 and β=2.8 and exhibited high correlation to SUV25 measures of tumor uptake. QRAS scores favor SUV25 followed by SUVP14 as optimal metrics of response to therapy. Additional studies are warranted to fully characterize the utility of SUV25 and µPERCIST SUVP14 as image metrics of response to therapy across a wide range of therapeutic regiments and PDX models.




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Early Detection in a Mouse Model of Pancreatic Cancer by Imaging DNA Damage Response Signalling

Rationale: Despite its widespread use in oncology, the PET radiotracer 18F-FDG is ineffective for improving early detection of pancreatic ductal adenocarcinoma (PDAC). An alternative strategy for early detection of pancreatic cancer involves visualisation of high-grade pancreatic intraepithelial neoplasias (PanIN-3), generally regarded as the non-invasive precursors of PDAC. The DNA damage response is known to be hyper-activated in late-stage PanINs. Therefore, we investigated whether the SPECT imaging agent, 111In-anti-H2AX-TAT, allows visualisation of the DNA damage repair marker H2AX in PanIN-3s in an engineered mouse model of PDAC, to facilitate early detection of PDAC. Methods: Genetically engineered KPC mice (KRasLSL.G12D/+; p53LSL.R172H/+; PdxCre) were imaged with 18F-FDG and 111In-anti-H2AX-TAT. PanIN/PDAC presence visualised by histology was compared with autoradiography and immunofluorescence. Separately, the survival of KPC mice imaged with 111In-anti-H2AX-TAT was evaluated. Results: In KPC mouse pancreata, H2AX expression was increased in high-grade PanINs, but not in PDAC, corroborating earlier results obtained from human pancreas sections. Uptake of 111In-anti-H2AX-TAT, but not 111In-IgG-TAT or 18F-FDG, within the pancreas was positively correlated with the age of KPC mice, which was correlated with the number of high-grade PanINs. 111In-anti-H2AX-TAT localises preferentially in high-grade PanIN lesions, but not in established PDAC. Younger, non-tumour-bearing KPC mice that show uptake of 111In-anti-H2AX-TAT in the pancreas survive significantly shorter than mice with physiological 111In-anti-H2AX-TAT uptake. Conclusion: 111In-anti-H2AX-TAT imaging allows non-invasive detection of DNA damage repair signalling upregulation in pre-invasive PanIN lesions and is a promising new tool to aid in the early detection and staging of pancreatic cancer.




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SUVmax-V for assessing treatment response in FDG-PET Imaging of Patient-Derived Tumor Xenografts involving Triple-Negative Breast Cancer




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Improved Alignment of PET and CT Images in Whole-Body PET/CT in Cases of Respiratory Motion During CT

Respiratory motion during the CT and PET parts of a PET/CT scan leads to imperfect alignment of anatomical features seen by the two modalities. In this work, we concentrate on the effects of motion during CT. We propose a novel approach for improving the alignment. Methods: Respiratory waveform data were gathered during the CT and PET parts of 28 PET/CT scans of cancer patients with 40 lesions up to 3 cm size in the lung or upper abdomen. PET list-mode data were reconstructed by three reconstruction methods: PET/static, PET/EX or end of expiration (OncoFreeze), and a novel PET/matched method that used both waveforms. The three methods were compared. The distance between tumor positions in PET and CT were characterized in visual interpretation by physicians as well as quantitatively. Tumor standardized uptake values (SUVmax and SUVpeak) were determined relative to SUV based on the static method. Image noise was evaluated in the liver and compared to PET/static. Results: In visual interpretation, the rate of good alignment was 13/21, 13/23 and 18/21 for PET/static, PET/EX and PET/matched methods, respectively, and the mean PET-CT distances were 3.5, 5.1 and 2.8 mm. In visual comparison with PET/EX, the rate of good alignment was increased in 1/10 and 7/10 cases for PET/static and PET/matched. SUVmax was on average 21% higher than PET/static when either PET/EX or PET/matched was used. SUVpeak was 12% higher. Image noise in the liver was 15% higher than static for the PET/EX method, and 40% higher for PET/matched; that is, noise was much lower than in gated PET. Conclusion: Acquiring respiratory waveforms both in PET (as in the current state of the art) and in CT (an unusual key step in this approach) has the potential to improve the alignment of PET and CT images. A proposed method for using this information was tested. Improved alignment was demonstrated.