nc Deletion of fatty acid transport protein 2 (FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPAR{alpha}-regulated genes [Lipids] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities. Full Article
nc COQ11 deletion mitigates respiratory deficiency caused by mutations in the gene encoding the coenzyme Q chaperone protein Coq10 [Lipids] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 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. Full Article
nc The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis [Cell Biology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Sperm head shaping is a key event in spermiogenesis and is tightly controlled via the acrosome–manchette network. Linker of nucleoskeleton and cytoskeleton (LINC) complexes consist of Sad1 and UNC84 domain–containing (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain proteins and form conserved nuclear envelope bridges implicated in transducing mechanical forces from the manchette to sculpt sperm nuclei into a hook-like shape. However, the role of LINC complexes in sperm head shaping is still poorly understood. Here we assessed the role of SUN3, a testis-specific LINC component harboring a conserved SUN domain, in spermiogenesis. We show that CRISPR/Cas9-generated Sun3 knockout male mice are infertile, displaying drastically reduced sperm counts and a globozoospermia-like phenotype, including a missing, mislocalized, or fragmented acrosome, as well as multiple defects in sperm flagella. Further examination revealed that the sperm head abnormalities are apparent at step 9 and that the sperm nuclei fail to elongate because of the absence of manchette microtubules and perinuclear rings. These observations indicate that Sun3 deletion likely impairs the ability of the LINC complex to transduce the cytoskeletal force to the nuclear envelope, required for sperm head elongation. We also found that SUN3 interacts with SUN4 in mouse testes and that the level of SUN4 proteins is drastically reduced in Sun3-null mice. Altogether, our results indicate that SUN3 is essential for sperm head shaping and male fertility, providing molecular clues regarding the underlying pathology of the globozoospermia-like phenotype. Full Article
nc Genetic Profile and Functional Proteomics of Anal Squamous Cell Carcinoma: Proposal for a Molecular Classification By feedproxy.google.com Published On :: 2020-04-01 Lucía Trilla-FuertesApr 1, 2020; 19:690-700Research Full Article
nc Organellar maps through proteomic profiling - a conceptual guide By feedproxy.google.com Published On :: 2020-04-28 Georg H H BornerApr 28, 2020; 0:R120.001971v1-mcp.R120.001971Review Full Article
nc Flow-induced reorganization of laminin-integrin networks within the endothelial basement membrane uncovered by proteomics By feedproxy.google.com Published On :: 2020-04-24 Eelke P. BéguinApr 24, 2020; 0:RA120.001964v1-mcp.RA120.001964Research Full Article
nc Seminal Plasma Proteome as an Indicator of Sperm Dysfunction and Low Sperm Motility By feedproxy.google.com Published On :: 2020-04-20 Yunlei LiApr 20, 2020; 0:RA120.002017v1-mcp.RA120.002017Research Full Article
nc Proteaphagy in mammalian cells can function independent of ATG5/ATG7 By feedproxy.google.com Published On :: 2020-04-16 Tatjana GoebelApr 16, 2020; 0:RA120.001983v1-mcp.RA120.001983Research Full Article
nc Robust summarization and inference in proteome-wide label-free quantification By feedproxy.google.com Published On :: 2020-04-22 Adriaan StickerApr 22, 2020; 0:RA119.001624v1-mcp.RA119.001624Research Full Article
nc Developments and Applications of Functional Protein Microarrays By feedproxy.google.com Published On :: 2020-04-17 Guan-Da SyuApr 17, 2020; 0:R120.001936v1-mcp.R120.001936Review Full Article
nc Identification of an Unconventional Subpeptidome Bound to the Behcet's Disease-associated HLA-B*51:01 that is Regulated by Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) By feedproxy.google.com Published On :: 2020-05-01 Liye ChenMay 1, 2020; 19:871-883Research Full Article
nc Human Hepatocyte Nuclear Factor 4-{alpha} Encodes Isoforms with Distinct Transcriptional Functions By feedproxy.google.com Published On :: 2020-05-01 Élie LambertMay 1, 2020; 19:808-827Research Full Article
nc Characterization of signaling pathways associated with pancreatic {beta}-cell adaptive flexibility in compensation of obesity-linked diabetes in db/db mice By feedproxy.google.com Published On :: 2020-04-07 Taewook KangApr 7, 2020; 0:RA119.001882v1-mcp.RA119.001882Research Full Article
nc DEqMS: a method for accurate variance estimation in differential protein expression analysis By feedproxy.google.com Published On :: 2020-03-23 Yafeng ZhuMar 23, 2020; 0:TIR119.001646v1-mcp.TIR119.001646Technological Innovation and Resources Full Article
nc Compliance Checklists No Longer Required at Initial Manuscript Submission By feedproxy.google.com Published On :: 2020-04-01 Alma L. BurlingameApr 1, 2020; 19:571-571Editorial Full Article
nc MaxQuant software for ion mobility enhanced shotgun proteomics By feedproxy.google.com Published On :: 2020-03-10 Nikita PrianichnikovMar 10, 2020; 0:TIR119.001720v1-mcp.TIR119.001720Technological Innovation and Resources Full Article
nc Rising to the challenge in the worst circumstances By feedproxy.google.com Published On :: Thu, 16 Apr 2020 14:28:47 +0000 In this era when we need to do everything possible to keep essential businesses operational, the people of the information security community have banded together in an inspirational effort to protect us all. Full Article Corporate coronavirus COVID-19 COVID-19 Cyber Threat Coalition CTI League Cyber Volunteers 19
nc Making the most of attending conferences By blogs.ams.org Published On :: Tue, 08 Oct 2019 16:54:02 +0000 In this blog by Julianne Vega, graduate student at University of Kentucky, Julianne tells us how to make the most of attending math conferences. If you are heading to a conference, challenge yourself! Your first conference may not be the … Continue reading → Full Article career advancement General Graduate School Uncategorized Undegraduates
nc Strengthening Urban Preparedness and Resilience Against Biological Threats in Accra By feedproxy.google.com Published On :: Wed, 23 Jan 2019 17:40:01 +0000 Invitation Only Research Event 1 March 2019 - 10:30am to 2 March 2019 - 3:00pm Chatham House, London Capacity to contain and respond to biological threats varies considerably across the world. Yet such preparedness is vital for prevention, impact-reduction and resilience in the face of biological events, whether they be natural or deliberate outbreaks.Chatham House is conducting a series of meetings to strengthen urban preparedness for, and resilience against, biological threats in African countries. This meeting will examine the preparedness and prevention mechanisms in Accra, reviewing the comprehensiveness of city-level preparedness. This meeting will focus on the formation and implementation of city-level action plans in the context of preparedness for managing biological threats. It will also explore how local authorities are contributing to this effort with their knowledge and expertise.Attendance at this event is by invitation only. Department/project International Security Programme, Strengthening Urban Preparedness and Resilience against Biological Threats Nilza Amaral Project Manager, International Security Programme Email Full Article
nc Transparency and Accountability for Drone Use: European Approaches By feedproxy.google.com Published On :: Thu, 07 Mar 2019 17:35:01 +0000 Invitation Only Research Event 11 March 2019 - 9:30am to 12 March 2019 - 12:30pm Chatham House With increased use of military drones in recent years there have also been many calls for greater transparency and accountability with regards to drone operations.This would allow for greater public understanding, particularly as the complex nature of military operations today intensifies difficulties in sustaining perceptions of the legitimate use of force.For example, in Europe, leading states rely on the US for drone platforms and for the infrastructure - such as military communication networks - that enable those operations, while the US also relies on airbases in European states to operate its drone programme.In addition, with reports that the US is loosening the rules on the use of drones, it is important to understand how European approaches to transparency and accountability may be affected by these developments.This workshop focuses on how European states can facilitate transparency to ensure accountability for drone use, as well as what the limits might be, considering both the complexity of military operations today and the need for achieving operational goals.With the US easing restrictions on export controls, the discussion also considers the role of regulation in ensuring accountability and prospects for developing common standards.Attendance at this event is by invitation only. Nilza Amaral Project Manager, International Security Programme Email Department/project International Security Programme, Policy Implications of Armed Drone Use Full Article
nc Cyber Insurance for Civil Nuclear Facilities: Risks and Opportunities By feedproxy.google.com Published On :: Wed, 08 May 2019 15:21:25 +0000 8 May 2019 This paper sets out a roadmap for how organizations in the civil nuclear sector can explore their options and review their cyber risk exposure. Read online Download PDF Éireann Leverett Senior Risk Researcher, University of Cambridge GettyImages-667179424.jpg The control room inside the Paks nuclear power plant in Hungary, 10 April 2017. Photo: Getty Images Civil nuclear facilities and organizations hold sensitive information on security clearances, national security, health and safety, nuclear regulatory issues and international inspection obligations. The sensitivity and variety of such data mean that products tailored for insuring the civil nuclear industry have evolved independently and are likely to continue to do so.‘Air-gaps’ – measures designed to isolate computer systems from the internet – need to be continually maintained for industrial systems. Yet years of evidence indicate that proper maintenance of such protections is often lacking (mainly because very real economic drivers exist that push users towards keeping infrastructure connected). Indeed, even when air-gaps are maintained, security breaches can still occur.Even if a particular organization has staff that are highly trained, ready and capable of handling a technological accident, hacking attack or incidence of insider sabotage, it still has to do business and/or communicate with other organizations that may not have the essentials of cybersecurity in place.Regardless of whether the choice is made to buy external insurance or put aside revenues in preparation for costly incidents, the approach to cyber risk calculation should be the same. Prevention is one part of the equation, but an organization will also need to consider the resources and contingency measures available to it should prevention strategies fail. Can it balance the likelihood of a hacker’s success against the maximum cost to the organization, and put aside enough capital and manpower to get it through a crisis?All civil nuclear facilities should consider the establishment of computer security incident response (CSIR) teams as a relevant concern, if such arrangements are not already in place. The existence of a CSIR team will be a prerequisite for any facility seeking to obtain civil nuclear cyber insurance.Preventing attacks such as those involving phishing and ransomware requires good cyber hygiene practices throughout the workforce. Reducing an organization’s ‘time to recovery’ takes training and dedication. Practising the necessary tasks in crisis simulations greatly reduces the likelihood of friction and the potential for error in a crisis. Department/project International Security Programme, Cyber and Nuclear Security Full Article
nc Cyber Governance in the Commonwealth: Towards Stability and Responsible State Behaviour in Cyberspace By feedproxy.google.com Published On :: Mon, 05 Aug 2019 14:05:02 +0000 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. Department/project International Security Programme Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email Full Article
Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email
nc Artificial Intelligence Prediction and Counterterrorism By feedproxy.google.com Published On :: Tue, 06 Aug 2019 10:46:13 +0000 9 August 2019 The use of AI in counterterrorism is not inherently wrong, and this paper suggests some necessary conditions for legitimate use of AI as part of a predictive approach to counterterrorism on the part of liberal democratic states. Download PDF Kathleen McKendrick British Army Officer, Former Visiting Research Fellow at Chatham House 2019-08-06-AICounterterrorism.jpg Surveillance cameras manufactured by Hangzhou Hikvision Digital Technology Co. at a testing station near the company’s headquarters in Hangzhou, China. Photo: Getty Images SummaryThe use of predictive artificial intelligence (AI) in countering terrorism is often assumed to have a deleterious effect on human rights, generating spectres of ‘pre-crime’ punishment and surveillance states. However, the well-regulated use of new capabilities may enhance states’ abilities to protect citizens’ right to life, while at the same time improving adherence to principles intended to protect other human rights, such as transparency, proportionality and freedom from unfair discrimination. The same regulatory framework could also contribute to safeguarding against broader misuse of related technologies.Most states focus on preventing terrorist attacks, rather than reacting to them. As such, prediction is already central to effective counterterrorism. AI allows higher volumes of data to be analysed, and may perceive patterns in those data that would, for reasons of both volume and dimensionality, otherwise be beyond the capacity of human interpretation. The impact of this is that traditional methods of investigation that work outwards from known suspects may be supplemented by methods that analyse the activity of a broad section of an entire population to identify previously unknown threats.Developments in AI have amplified the ability to conduct surveillance without being constrained by resources. Facial recognition technology, for instance, may enable the complete automation of surveillance using CCTV in public places in the near future.The current way predictive AI capabilities are used presents a number of interrelated problems from both a human rights and a practical perspective. Where limitations and regulations do exist, they may have the effect of curtailing the utility of approaches that apply AI, while not necessarily safeguarding human rights to an adequate extent.The infringement of privacy associated with the automated analysis of certain types of public data is not wrong in principle, but the analysis must be conducted within a robust legal and policy framework that places sensible limitations on interventions based on its results.In future, broader access to less intrusive aspects of public data, direct regulation of how those data are used – including oversight of activities by private-sector actors – and the imposition of technical as well as regulatory safeguards may improve both operational performance and compliance with human rights legislation. It is important that any such measures proceed in a manner that is sensitive to the impact on other rights such as freedom of expression, and freedom of association and assembly. Department/project Digital Society Initiative, International Security Programme, UK Defence Full Article
nc Who’s Afraid of Huawei? Understanding the 5G Security Concerns By feedproxy.google.com Published On :: Fri, 06 Sep 2019 09:55:03 +0000 9 September 2019 Emily Taylor Associate Fellow, International Security Programme @etaylaw LinkedIn Emily Taylor examines the controversy around the Chinese tech giant’s mobile broadband equipment and the different approaches taken by Western countries. 2019-09-06-Huawei.jpg Huawei's Ox Horn campus in Dongguan, China. Photo: Getty Images. As countries move towards the fifth generation of mobile broadband, 5G, the United States has been loudly calling out Huawei as a security threat. It has employed alarmist rhetoric and threatened to limit trade and intelligence sharing with close allies that use Huawei in their 5G infrastructure.While some countries such as Australia have adopted a hard line against Huawei, others like the UK have been more circumspect, arguing that the risks of using the firm’s technology can be mitigated without forgoing the benefits.So, who is right, and why have these close allies taken such different approaches?The risksLong-standing concerns relating to Huawei are plausible. There are credible allegations that it has benefitted from stolen intellectual property, and that it could not thrive without a close relationship with the Chinese state.Huawei hotly denies allegations that users are at risk of its technology being used for state espionage, and says it would resist any order to share information with the Chinese government. But there are questions over whether it could really resist China’s stringent domestic legislation, which compels companies to share data with the government. And given China’s track record of using cyberattacks to conduct intellectual property theft, there may be added risks of embedding a Chinese provider into critical communications infrastructure.In addition, China’s rise as a global technological superpower has been boosted by the flow of financial capital through government subsidies, venture and private equity, which reveal murky boundaries between the state and private sector for domestic darlings. Meanwhile, the Belt and Road initiative has seen generous investment by China in technology infrastructure across Africa, South America and Asia.There’s no such thing as a free lunch or a free network – as Sri Lanka discovered when China assumed shares in a strategic port in return for debt forgiveness; or Mexico when a 1% interest loan for its 4G network came on the condition that 80% of the funding was spent with Huawei.Aside from intelligence and geopolitical concerns, the quality of Huawei’s products represents a significant cyber risk, one that has received less attention than it deserves.On top of that, 5G by itself will significantly increase the threat landscape from a cybersecurity perspective. The network layer will be more intelligent and adaptable through the use of software and cloud services. The number of network antennae will increase by a factor of 20, and many will be poorly secured ‘things’; there is no need for a backdoor if you have any number of ‘bug doors’.Finally, the US is threatening to limit intelligence sharing with its closest allies if they adopt Huawei. So why would any country even consider using Huawei in their 5G infrastructure?Different situationsThe truth is that not every country is free to manoeuvre; 5G technology will sit on top of existing mobile infrastructure.Australia and the US can afford to take a hard line: their national infrastructure has been largely Huawei-free since 2012. However, the Chinese firm is deeply embedded in other countries’ existing structures – for example, in the UK, Huawei has provided telecommunications infrastructure since 2005. Even if the UK decided tomorrow to ditch Huawei, it cannot just rip up existing 4G infrastructure. To do so would cost a fortune, risk years of delay in the adoption of 5G and limit competition in 5G provisioning.As a result, the UK has adopted a pragmatic approach resulting from years of oversight and analysis of Huawei equipment, during which it has never found evidence of malicious Chinese state cyber activity through Huawei.At the heart of this process is the Huawei Cyber Security Evaluation Centre, which was founded in 2010 as a confidence-building measure. Originally criticized for ‘effectively policing itself’, as it was run and staffed entirely by Huawei, the governance has now been strengthened, with the National Cyber Security Centre chairing its oversight board.The board’s 2019 report makes grim reading, highlighting ‘serious and system defects in Huawei’s software engineering and cyber security competence’. But it does not accuse the company of serving as a platform for state-sponsored surveillance.Similar evidence-based policy approaches are emerging in other countries like Norway and Italy. They offer flexibility for governments, for example by limiting access to some contract competition through legitimate and transparent means, such as security reviews during procurement. The approaches also raise security concerns (both national and cyber) to a primary issue when awarding contracts – something that was not always done in the past, when price was the key driver.The UK is also stressing the need to manage risk and increase vendor diversity in the ecosystem to avoid single points of failure. A further approach that is beginning to emerge is to draw a line between network ‘core’ and ‘periphery’ components, excluding some providers from the more sensitive ‘core’. The limited rollouts of 5G in the UK so far have adopted multi-provider strategies, and only one has reportedly not included Huawei kit.Managing the risks to cyber security and national security will become more complex in a 5G environment. In global supply chains, bans based on the nationality of the provider offer little assurance. For countries that have already committed to Huawei in the past, and who may not wish to be drawn into an outright trade war with China, these moderate approaches offer a potential way forward. Full Article
nc EU–US Relations on Internet Governance By feedproxy.google.com Published On :: Thu, 14 Nov 2019 16:12:28 +0000 14 November 2019 As internet governance issues emerge in the wake of innovations such as the Internet of Things and advanced artificial intelligence, there is an urgent need for the EU and US to establish a common, positive multi-stakeholder vision for regulating and governing the internet. Read online Download PDF Emily Taylor Associate Fellow, International Security Programme @etaylaw LinkedIn Stacie Hoffmann Internet Policy and Cybersecurity Consultant, Oxford Information Labs 2019-11-14-EUUSInternet.jpg Server room network cables in New York City, November 2014. Photo: Michael Bocchieri/Staff/Getty. Political, economic, sociological and technological factors are poised to challenge EU and US ideological positions on internet governance, which will make it difficult to find consensus and common ground in the years to come.The EU and US share core values and perspectives relating to internet governance, such as openness, freedom and interoperability, as well as a human rights framework for cybersecurity. There have been many examples of successful multi-stakeholder cooperation between the EU and US, including the Internet Assigned Numbers Authority (IANA) transition and the European Dialogue on Internet Governance (EuroDIG).There are also subtle differences between the EU and US, and each has different reasons to support multi-stakeholderism. Cases that highlight growing tensions in EU–US coordination on internet governance include the controversies surrounding the EU General Data Protection Regulation (GDPR), the WHOIS system that governs domain name registration data, and the board of the Internet Corporation for Assigned Names and Numbers (ICANN), which undermined an independent cybersecurity review.Internet governance is becoming more complex, with a multiplicity of actors and no obvious authority for important emerging issues. Additionally, the rise of China and its authoritarian vision for the future of the internet is a threat to the current internet governance institutions that have been shaped by and reflect Western values.To bridge ideological gaps the EU and US should build capacity between likeminded stakeholders, create a taskforce on effective multi-stakeholder internet governance, and work through non-governmental stakeholders to improve participation. Department/project International Security Programme, Internet Governance Full Article
nc Building LGBTIQ+ Inclusivity in the Armed Forces, 20 Years After the Ban Was Lifted By feedproxy.google.com Published On :: Thu, 16 Jan 2020 12:27:18 +0000 16 January 2020 Will Davies Army Chief of General Staff Research Fellow, International Security Programme @williamhldavies LinkedIn Change was slow to come but progress has since been swift. Not only can a continuing focus on inclusivity benefit service people and the organization, it is also an essential element of a values-based foreign policy. 2020-01-16-Westminster.jpg Crew members from HMS Westminster march through Admiralty Arch as they exercise their freedom of the city in August 2019 in London. Photo: Getty Images. The new UK government will conduct a review of foreign, security and defence policy in 2020. If the UK decides to use values as a framework for foreign policy this needs to be reflected in its armed forces. One area where this is essential is continuing to deepen inclusivity for LGBTIQ+ personnel, building on the progress made since the ban on their service was lifted in 2000.I witnessed the ban first-hand as a young officer in the British Army in 1998. As the duty officer I visited soldiers being held in the regimental detention cells to check all was well. One day a corporal, who I knew, was there awaiting discharge from the army having been convicted of being gay. On the one hand, here was service law in action, which was officially protecting the army’s operational effectiveness and an authority not to be questioned at my level. On the other, here was an excellent soldier in a state of turmoil and public humiliation. How extreme this seems now.On 12 January 2000 Tony Blair’s Labour government announced an immediate lifting of the ban for lesbian, gay and bisexual personnel (LGB) and introduced a new code of conduct for personal relationships. (LGB is the term used by the armed forces to describe those personnel who had been banned prior to 2000.) This followed a landmark ruling in a case taken to the European Court of Human Rights in 1999 by four LGB ex-service personnel – supported by Stonewall – who had been dismissed from service for their sexuality.Up to that point the Ministry of Defence's long-held position had been that LGB personnel had a negative impact on the morale and cohesion of a unit and damaged operational effectiveness. Service personnel were automatically dismissed if it was discovered they were LGB, even though homosexuality had been decriminalized in the UK by 1967.Proof that the armed forces had been lagging behind the rest of society was confirmed by the positive response to the change among service personnel, despite a handful of vocal political and military leaders who foresaw negative impacts. The noteworthy service of LGBTIQ+ people in Iraq and Afghanistan only served to debunk any residual myths.Twenty years on, considerable progress has been made and my memories from 1998 now seem alien. This is a story to celebrate – however in the quest for greater inclusivity there is always room for improvement.Defence Minister Johnny Mercer last week apologized following recent calls from campaign group Liberty for a fuller apology. In December 2019, the Ministry of Defence announced it was putting in place a scheme to return medals stripped from veterans upon their discharge.The armed forces today have a range of inclusivity measures to improve workplace culture including assessments of workplace climate and diversity networks supported by champions drawn from senior leadership.But assessing the actual lived experience for LGBTIQ+ people is challenging due to its subjectivity. This has not been helped by low participation in the 2015 initiative to encourage people to declare confidentially their sexual orientation, designed to facilitate more focused and relevant policies. As of 1 October 2019, only 20.3 per cent of regular service people had declared a sexual orientation.A measure of positive progress is the annual Stonewall Workplace Equality Index, the definitive benchmarking tool for employers to measure their progress on LGBTIQ+ inclusion in the workplace; 2015 marked the first year in which all three services were placed in the top 100 employers in the UK and in 2019 the Royal Navy, British Army and Royal Air Force were placed 15th=, 51st= and 68th respectively.Nevertheless, LGBTIQ+ service people and those in other protected groups still face challenges. The 2019 Ministry of Defence review of inappropriate behaviour in the armed forces, the Wigston Report, concluded there is an unacceptable level of sexual harassment, bullying and discrimination. It found that 26-36% of LGBTIQ+ service people have experienced negative comments or conduct at work because of their sexual orientation.The Secretary of State for Defence accepted the report’s 36 recommendations on culture, incident reporting, training and a more effective complaints system. Pivotal to successful implementation will be a coherent strategy driven by fully engaged leaders.Society is also expecting ever higher standards, particularly in public bodies. The armed forces emphasise their values and standards, including ‘respect for others’, as defining organisational characteristics; individuals are expected to live by them. Only in a genuinely inclusive environment can an individual thrive and operate confidently within a team.The armed forces also recognize as a priority the need to connect to and reflect society more closely in order to attract and retain talent from across all of society. The armed forces’ active participation in UK Pride is helping to break down barriers in this area.In a post-Brexit world, the UK’s values, support for human rights and reputation for fairness are distinctive strengths that can have an impact on the world stage and offer a framework for future policy. The armed forces must continue to push and promote greater inclusivity in support. When operating overseas with less liberal regimes, this will be sensitive and require careful handling; however it will be an overt manifestation of a broader policy and a way to communicate strong and consistent values over time.The armed forces were damagingly behind the times 20 years ago. But good progress has been made since. Inclusion initiatives must continue to be pushed to bring benefits to the individual and the organization as well as demonstrate a values-based foreign policy. Full Article
nc POSTPONED: Working Towards Cyber Resilience in the GCC: Opportunities and Challenges By feedproxy.google.com Published On :: Fri, 14 Feb 2020 14:10:01 +0000 Invitation Only Research Event 12 March 2020 - 9:00am to 5:00pm Muscat, Oman The GCC states have invested significantly in cybersecurity and have made large strides in protecting governments, businesses and individuals from cyber threats, with the aim of delivering on their ambitious national strategies and future visions. However, several challenges to cybersecurity and cyber resilience in the region persist, putting those ambitious plans at risk.These challenges include the uneven nature of cybersecurity protections, the incomplete implementation of cybersecurity strategies and regulations, and the issues around international cooperation. Such challenges mean that GCC states need to focus on the more difficult task of cyber resilience, in addition to the simpler initial stages of cybersecurity capacity-building, to ensure they harness the true potential of digital technologies and mitigate associated threats.Set against this background, this workshop will explore opportunities and challenges to cyber resilience in the GCC focusing on four main pillars:1. Cyber resilience: in concept and in practice2. Building an effective cybersecurity capacity3. The potential of regional and international cooperation to cyber resilience4. Deterrence and disruption: different approachesThis event will be held in collaboration with the Arab Regional Cybersecurity Centre (ARCC) and OMAN CERT.PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Event attributes Chatham House Rule Department/project International Security Programme Esther Naylor Research Assistant, International Security Programme +44 (0)20 7314 3628 Email Full Article
nc Deterrence Perspectives in the 21st Century By feedproxy.google.com Published On :: Fri, 28 Feb 2020 09:36:23 +0000 The aim of this project is to provide a space to explore creative/disruptive ideas in order to make headway on perspectives concerning deterrence. This will encourage ‘responsible disruption’ in the nuclear field. Concerns about transatlantic security are high following the US 2018 Nuclear Posture Review and its interpretation of the Russian doctrine, the demise of the Intermediate Range Nuclear Forces Treaty (INF), the uncertainty surrounding the potential extension of the New Strategic Arms Reduction Treaty (New START), and Russian deployment of Avangard hypersonic, nuclear-capable missile systems.Emerging technologies, especially quantum technologies, jeopardize the reliability of existing encryption measures. Some of the most sophisticated cyber attacks are already assisted by artificial intelligence. The possibility that nuclear weapons systems can be interfered with both during conflict and peacetime by these technologies, without the knowledge of the possessor state, raises questions on the reliability and integrity of these systems, with implications for military decision-making, particularly to deterrence policy.These issues and more indicate the changes in the security landscape that have a bearing on the future of nuclear deterrence.This project is supported by the Hiroshima Prefecture and Government of Ireland. Latest (1) Research paper Perspectives on Nuclear Deterrence in the 21st Century 20 April 2020 Research & Publications (1) Research paper Perspectives on Nuclear Deterrence in the 21st Century 20 April 2020 Full Article
nc Perspectives on Nuclear Deterrence in the 21st Century By feedproxy.google.com Published On :: Sun, 19 Apr 2020 19:32:28 +0000 20 April 2020 Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in the 21st century. Researchers at Chatham House have worked with eight experts to produce this collection of essays examining four contested themes in contemporary policymaking on deterrence. Read online Download PDF Dr Beyza Unal Senior Research Fellow, International Security Programme @beyzaunal Google Scholar Yasmin Afina Research Assistant, International Security Programme @afinayasmin LinkedIn Dr Patricia Lewis Research Director, Conflict, Science & Transformation; Director, International Security Programme @PatriciaMary Dr John Borrie Associate Fellow, International Security Programme Google Scholar Dr Jamie Shea Associate Fellow, International Security Programme LinkedIn Peter Watkins Associate Fellow, International Security Programme LinkedIn Dr Maria Rost Rublee Associate Professor of International Relations, Monash University Cristina Varriale Research Fellow in Proliferation and Nuclear Policy, RUSI Dr Tanya Ogilvie-White Adjunct Senior Fellow, Griffith Asia Institute, Griffith University Dr Andrew Futter Associate Professor of International Politics, University of Leicester Christine Parthemore Chief Executive Officer, Council on Strategic Risks (CSR) 2020-04-20-NuclearDeterrence.jpeg Royal Navy Vanguard Class submarine HMS Vigilant returning to HMNB Clyde after extended deployment. The four Vanguard-class submarines form the UK's strategic nuclear deterrent force. Photo: Ministry of Defence. SummaryThis collection of essays explores, from the perspectives of eight experts, four areas of deterrence theory and policymaking: the underlying assumptions that shape deterrence practice; the enduring value of extended deterrence; the impact of emerging technologies; and the ‘blurring’ of the lines between conventional and nuclear weapons.Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in security and defence in the 21st century, given the larger number of nuclear actors in a less binary geopolitical context. It is clear that a number of present factors challenge the overall credibility of ‘classical’ nuclear deterrence, meaning that in-depth analysis is now needed.Uncertainty as to the appetite to maintain the current nuclear weapons policy architecture looms large in discussions and concerns on global and regional security. The demise of the Intermediate-Range Nuclear Forces Treaty, doubts over the potential extension of the New Strategic Arms Reduction Treaty, heightened regional tensions in Northeast and South Asia, together with the current and likely future risks and challenges arising from global technological competition, making it all the more urgent to examine long-held assumptions in the real-world context.Extended deterrence practices differ from region to region, depending on the domestic and regional landscape. Increased focus on diplomatic capabilities to reduce risks and improve the long-term outlook at regional level, including by spearheading new regional arms-control initiatives, may be a viable way forward. Addressing the bigger picture – notably including, on the Korean peninsula, Pyongyang’s own threat perception – and the links between conventional and nuclear missile issues will need to remain prominent if long-term and concrete changes are to take hold.Most states have long held nuclear weapons to be ‘exceptional’: their use would represent a dramatic escalation of a conflict that must never be attained. Latterly, however, some officials and scholars have made the case that the impact of the use of a low-yield nuclear weapon would not be entirely distinct from that of a large-scale conventional attack. This blurring of lines between conventional and nuclear deterrence strips nuclear weapons of their exceptional nature, in a context in which states are faced with diverse, complex and concurrent threats from multiple potential adversaries that are able to synchronize non-military and military options, up to and including nuclear forces. The use of nuclear weapons risks becoming a ‘new normal’, potentially reducing the threshold for use – to cyberattacks, for example. This has direct implications for discussions around strategic stability. While emerging technologies may offer tremendous opportunities in the modernization of nuclear weapons, they also present major risks and destabilizing challenges. Artificial intelligence, automation, and other developments in the cyber sphere affect dynamics on both the demand and supply sides of the nuclear deterrence equation. States and alliance such as NATO must adapt their deterrence thinking in light of these technological developments, and define their primary purpose and priorities in this shifting security context. Resilience planning, adaptation to the evolving security environment, threat anticipation, and consistent crisis management and incident response – as well as thinking about the mitigation measures necessary to prevent conflict escalation should deterrence fail – will all be critical in upholding nuclear deterrence as both policy and practice. Department/project International Security Programme, Deterrence Perspectives in the 21st Century Full Article
nc Prospects for Reforming Libya’s Economic Governance: Ways Forward By feedproxy.google.com Published On :: Mon, 27 Jan 2020 15:45:02 +0000 Invitation Only Research Event 6 February 2020 - 10:30am to 12:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Jason Pack, Non-Resident Fellow, Middle East InstituteTim Eaton, Senior Research Fellow, Middle East and North Africa Programme, Chatham HouseChair: Elham Saudi, Director, Lawyers for Justice Libya There is a broad consensus that Libya’s rentier, patronage-based system of governance is a driver, and not only a symptom, of Libya’s continuing conflict. The dysfunction of Libya’s economic system of governance has been exacerbated by the governance split that has prevailed since 2014 whereby rival administrations of state institutions have emerged. Despite these challenges, a system of economic interdependence, whereby forces aligned with Field Marshal Haftar control much of the oil and gas infrastructure and the UN-backed Government of National Accord controls the means of financial distribution, has largely prevailed. Yet, at the time of writing, this is under threat: a damaging oil blockade is being implemented by forces aligned with Haftar and those state institutions that do function on a national basis are finding it increasingly difficult to avoid being dragged into the conflict.This roundtable will bring together analysts and policymakers to discuss these dynamics and look at possible remedies. Jason Pack, non-resident fellow at the Middle East Institute, will present the findings of his latest paper on the issue which recommends the formation of 'a Libyan-requested and Libyan-led International Financial Commission vested with the requisite authorities to completely restructure the economy.' Tim Eaton, who has been leading Chatham House’s work on Libya’s conflict economy, supporting UNSMIL’s efforts in this field, will act as respondent.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme, Libya’s Conflict Economy Full Article
nc Lebanon Is Paying the Cost of Its Dysfunctional Politics By feedproxy.google.com Published On :: Wed, 26 Feb 2020 05:27:10 +0000 26 February 2020 Nadim Shehadi Associate Fellow, Middle East and North Africa Programme @Confusezeus A series of fights to political stalemate have led its economy to the brink and cut it off from its natural economic partners in the Gulf. 2020-02-25-Leb1.jpg Protests against economic conditions and government inaction turned violent in January. Photo: Getty Images. To understand Lebanon’s financial collapse, look to its politics.The country has been deeply damaged by an increasingly dysfunctional political system. A series of compromises have alienated it from its main markets in the Gulf and strangled its economy; anyone that has glanced at fluctuations in Lebanese bank deposits over the last 10 years can see the correlation.Imagine if Boris Johnson or Donald Trump were obliged to form joint governments with Jeremy Corbyn or Bernie Sanders. The result would be paralysis and lack of accountability as each party pulls the country in opposite directions and blames the other for the state of limbo. This has been the state of affairs in Lebanon since the Doha agreement of 2008. That agreement followed an 18-month siege that paralyzed Beirut and an attack on the city by Hezbollah’s ‘black shirts’. The Doha formula imposed governments of national unity between Prime Minister Saad Hariri’s pro-Saudi camp and Hezbollah’s pro-Iran camp and their respective internal allies.The pattern was set: each period of subsequent paralysis was followed by further compromise as the tug of war pulled the country away from its principal economic partners, the Arab Gulf states, with the regional balance of power tilting towards Hezbollah. It was not supposed to be like this. The Baabda Declaration in June 2012, reached after a process of national dialogue, was meant to secure Lebanon’s neutrality in regional conflicts, with both sides promising to hold back on external alliances and coexist despite difference over major regional issues like the war in Syria, the standoff between the US and Iran or relations with Israel or the Gulf states.This has worn away. The Baabda declaration itself became a sham when Hezbollah inserted itself into the war in Syria in support of the Assad regime and overtly got involved in Iraq and Yemen as an Iranian proxy. This was followed by Saudi opposition to concessions by Hariri that led to the election of General Michel Aoun, an ally of Hezbollah, as president in October 2016; again, after a political paralysis that lasted 29 months with no active government and no head of state. The Saudis were also furious when President Aoun’s son-in-law, Foreign Minister Gebran Bassil, abstained from condemning the burning of the Saudi embassy in Tehran at an Arab League meeting in Cairo in January 2016, citing the need to preserve national unity.Fearing that he was simply providing Hezbollah with protection in the guise of compromise, the Saudis pressured Hariri to resign in November 2017 during a trip to Riyadh, but he later challenged that by retracting on his resignation when back in Beirut. Lebanon was caught between two sides, and as the regional conflict intensified from tension to open confrontation, neutrality was no longer an option.Gulf connectionsAn estimated 350,000 Lebanese expats live and work in Saudi Arabia, the UAE, Qatar and Kuwait. These countries are also the main clients for Lebanese contractors, consultants and advertising companies, some of which have offices there. The domestic tourism industry relies heavily on Arab Gulf visitors and they are a principal source of foreign investments especially in the real estate sector.Lebanon also enjoyed a certain degree of political and economic protection from the US and the Gulf, and Hezbollah benefited indirectly from that protection, as it also shielded it to a certain degree from sanctions.The deterioration of relations meant that the country was cut off by its Gulf partners. This was manifested in travel bans for Gulf Cooperation Council (GCC) nationals to Lebanon and a decrease in investments and bank deposits, as well as a decrease in remittances from Lebanese expats, partly because of economic crisis in the Gulf countries themselves.Saudi Arabia withdrew $4 billion of aid to the Lebanese army and internal security forces, and no aid or deposits were forthcoming as the economic and financial situation deteriorated. The costs to the Lebanese economy include the opportunity cost created by the annual threat of war with Israel, after which trips are cancelled and projects postponed. Hezbollah also controls a section of Beirut port where it pays no duty or taxes. Add to that the economic fallout from the war in Syria, such as the impact on exports, the inflow of refugees and the cost of Hezbollah’s involvement.The burden of these political factors is difficult to estimate but it constitutes the ransom that the Lebanese economy bears as a cost of the compromise. This is not to absolve Lebanese politicians from corruption or bankers of mismanagement but to add that political factors cannot be ignored.The cumulative cost and economic impact of being cut off from its main economic partner eventually bankrupted the country. The fiscal and financial aspects, with Lebanon’s inability to service its debt, are but a reflection of these political factors. In the long run, the key to avoiding complete collapse is to restore relations with the GCC and free Lebanon from that very costly grip. Full Article
nc Unpacking the role of religion in political transnationalism: the case of the Shi'a Iraqi diaspora since 2003 By feedproxy.google.com Published On :: Wed, 04 Mar 2020 12:58:04 +0000 4 March 2020 , Volume 96, Number 2 Oula Kadhum Read Online This article explores the role of religion in political transnationalism using the case of the Shi'a Iraqi diaspora since 2003. The article focuses on three areas that capture important trends in Shi'a transnationalism and their implications for transnational Shi'a identity politics. These include Shi'a diasporic politics, transnational Shi'a civic activism, and the cultural production of Iraqi Shi'a identity through pilgrimages, rituals and new practices. It is argued that understanding Shi'a Islam and identity formation requires adopting a transnational lens. The evolution of Shi'a Islam is not only a result of the dictates of the Shi'a clerical centres, and how they influence Shi'a populations abroad, but also the transnational interrelationships and links to holy shrine cities, Shi'i national and international politics, humanitarianism and commemorations and rituals. The article demonstrates that Shi'a political transnationalism is unexceptional in that it echoes much of the literature on diasporic politics and development where diaspora involve themselves from afar in the politics and societies of their countries of origin. At the same time, it shows the exceptionalism of Shi'a diasporic movements, in that their motivations and mobilizations are contributing to the reification of sectarian geographical and social borders, creating a transnationalism that is defined by largely Shi'a networks, spaces, actors and causes. The case of Shi'a political transnationalism towards Iraq shows that this is increasing the distance between Shi'is and Iraq's other communities, simultaneously fragmenting Iraq's national unity while deepening Shi'a identity and politics both nationally and supra-nationally. Full Article
nc POSTPONED: The Development of Libyan Armed Groups since 2014: Community Dynamics and Economic Interests By feedproxy.google.com Published On :: Wed, 04 Mar 2020 14:15:01 +0000 Invitation Only Research Event 18 March 2020 - 9:00am to 10:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Abdul Rahman Alageli, Associate Fellow, MENA Programme, Chatham HouseEmaddedin Badi, Non-Resident Scholar, Middle East InstituteTim Eaton, Senior Research Fellow, MENA Programme Chatham HouseValerie Stocker, Independent Researcher Since the overthrow of the regime of Muammar Gaddafi in 2011, Libya’s multitude of armed groups have followed a range of paths. While many of these have gradually demobilized, others have remained active, and others have expanded their influence. In the west and south of the country, armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks.In the east, the Libyan Arab Armed Forces projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will need to address the fears, grievances and desires of the surrounding communities, even while the development of armed groups’ capacities dilutes their accountability to those communities.This roundtable will discuss the findings of a forthcoming Chatham House research paper, ‘The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests’, which presents insights from over 200 interviews of armed actors and members of local communities and posits how international policymakers might seek to curtail the continued expansion of the conflict economy.PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme, Countering Conflict Economies in MENA, Libya’s Conflict Economy Georgia Cooke Project Manager, Middle East and North Africa Programme +44 (0)20 7957 5740 Email Full Article
nc The Development of Libyan Armed Groups Since 2014: Community Dynamics and Economic Interests By feedproxy.google.com Published On :: Mon, 16 Mar 2020 17:25:16 +0000 17 March 2020 This paper explores armed group–community relations in Libya and the sources of revenue that have allowed armed groups to grow in power and influence. It draws out the implications for policy and identifies options for mitigating conflict dynamics. Read online Download PDF Tim Eaton Senior Research Fellow, Middle East and North Africa Programme @el_khawaga LinkedIn Abdul Rahman Alageli Associate Fellow, Middle East and North Africa Programme @abdulrahmanlyf Emadeddin Badi Policy Leader Fellow, School of Transnational Governance, European University Institute Mohamed Eljarh Co-founder and CEO, Libya Outlook Valerie Stocker Researcher Amru_24-2_13.jpg Fighters of the UN-backed Government of National Accord patrol in Ain Zara suburb in Tripoli, February 2020. Photo: Amru Salahuddien SummaryLibya’s multitude of armed groups have followed a range of paths since the emergence of a national governance split in 2014. Many have gradually demobilized, others have remained active, and others have expanded their influence. However, the evolution of the Libyan security sector in this period remains relatively understudied. Prior to 2011, Libya’s internal sovereignty – including the monopoly on force and sole agency in international relations – had been personally vested in the figure of Muammar Gaddafi. After his death, these elements of sovereignty reverted to local communities, which created armed organizations to fill that central gap. National military and intelligence institutions that were intended to protect the Libyan state have remained weak, with their coherence undermined further by the post-2014 governance crisis and ongoing conflict. As a result, the most effective armed groups have remained localized in nature; the exception is the Libyan Arab Armed Forces (LAAF), which has combined and amalgamated locally legitimate forces under a central command.In the west and south of the country, the result of these trends resembles a kind of inversion of security sector reform (SSR) and disarmament, demobilization and reintegration (DDR): the armed groups have used their state affiliation to co-opt the state and professionals from the state security apparatus into their ranks; and have continued to arm, mobilize and integrate themselves into the state’s security apparatus without becoming subservient to it. In the eastern region, the LAAF projects a nationalist narrative yet is ultimately subservient to its leader, Field Marshal Khalifa Haftar. The LAAF has co-opted social organizations to dominate political and economic decision-making.The LAAF has established a monopoly over the control of heavy weapons and the flow of arms in eastern Libya, and has built alliances with armed groups in the east. Armed groups in the south have been persuaded to join the LAAF’s newly established command structure. The LAAF’s offensive on the capital, which started in April 2019, represents a serious challenge to armed groups aligned with the Tripoli-based Government of National Accord (GNA). The fallout from the war will be a challenge to the GNA or any future government, as groups taking part in the war will expect to be rewarded. SSR is thus crucial in the short term: if the GNA offers financial and technical expertise and resources, plus legal cover, to armed groups under its leadership, it will increase the incentive for armed groups to be receptive to its plans for reform.Prevailing policy narratives presuppose that the interests of armed actors are distinct from those of the communities they claim to represent. Given the degree to which most armed groups are embedded in local society, however, successful engagement will necessarily rely on addressing the fears, grievances and desires of the surrounding communities. Yet the development of armed groups’ capacities, along with their increasing access to autonomous means of generating revenue, has steadily diluted their accountability to local communities. This process is likely to be accelerated by the ongoing violence around Tripoli.Communities’ relationship to armed groups varies across different areas of the country, reflecting the social, political, economic and security environment:Despite their clear preference for a more formal, state-controlled security sector, Tripoli’s residents broadly accept the need for the presence of armed groups to provide security. The known engagement of the capital’s four main armed groups in criminal activity is a trade-off that many residents seem able to tolerate, providing that overt violence remains low. Nonetheless, there is a widespread view that the greed of Tripoli’s armed groups has played a role in stoking the current conflict.In the east, many residents appear to accept (or even welcome) the LAAF’s expansion beyond the security realm, provided that it undertakes these roles effectively. That said, such is the extent of LAAF control that opposition to the alliance comes at a high price.In the south, armed groups draw heavily on social legitimacy, acting as guardians of tribal zones of influence and defenders of their respective communities against outside threats, while also at times stoking local conflicts. Social protections continue to hold sway, meaning that accountability within communities is also limited.To varying extents since 2014, Libya’s armed groups have developed networks that enmesh political and business stakeholders in revenue-generation models:Armed groups in Tripoli have compensated for reduced financial receipts from state budgets by cultivating unofficial and illicit sources of income. They have also focused on infiltrating state institutions to ensure access to state budgets and contracts dispersed in the capital.In the east of the country, the LAAF has developed a long-term strategy to dominate the security, political and economic spheres through the establishment of a quasi-legal basis for receiving funds from Libya’s rival state authorities. It has supplemented this with extensive intervention in the private sector. External patronage supports military operations, but also helps to keep this financial system, based on unsecured debt, afloat.In the south, limited access to funds from the central state has spurred armed groups to become actively involved in the economy. This has translated into the taxation of movement and the imposition of protection fees, particularly on informal (and often illicit) activity.Without real commitment from international policymakers to enforcing the arms embargo and protecting the economy from being weaponized, Libya will be consigned to sustained conflict, further fragmentation and potential economic collapse. Given the likely absence of a political settlement in the short term, international policymakers should seek to curtail the continued expansion of the conflict economy by reducing armed groups’ engagement in economic life.In order to reduce illicit activities, international policymakers should develop their capacity to identify and target chokepoints along illicit supply chains, with a focus on restraining activities and actors in closest proximity to violence. Targeted sanctions against rent maximizers (both armed and unarmed) is likely to be the most effective strategy. More effective investigation and restraint of conflict economy actors will require systemic efforts to improve transparency and enhance the institutional capacity of anti-corruption authorities. International policymakers should also support the development of tailored alternative livelihoods that render conflict economy activities less attractive. Department/project Middle East and North Africa Programme, Chaos States, Countering Conflict Economies in MENA, Libya’s Conflict Economy Full Article
nc Virtual Roundtable: Iraq in Uncertain Times By feedproxy.google.com Published On :: Thu, 26 Mar 2020 10:40:01 +0000 Invitation Only Research Event 30 March 2020 - 2:00pm to 3:30pm Event participants Toby Dodge, Associate Fellow, MENA Programme, Chatham HouseMac Skelton, Director, IRIS, American University of Iraq-SulaimaniAhmed Tabaqchali, Chief Investment Officer, AFC Iraq FundHanaa Edwar, Co-founder and Chairperson, Iraqi Al-Amal AssociationChair: Renad Mansour, Senior Research Fellow, MENA Programme, Chatham House The first months of 2020 have proven tumultuous for Iraq. The US killing of Iranian General Qassem Soleimani in January threatened to engulf the region in war and led to continued tit-for-tat violence between the US and Iran that has become almost a daily reality in Baghdad.Amid the ongoing protests that since last October have challenged the social contract and led to a violent response claiming 600 deaths and injuring tens of thousands, the government is still without a prime minister after Adil abd al-Mehdi's resignation in November 2019, leaving the country directionless.Most recently, the spread of COVID-19 threatens to expose a mismanaged healthcare system. At the same time, the rapid fall in the price of oil has impacted the government's ability to respond to or cope with these crises.At this virtual roundtable, part of the Chatham House Iraq Initiative, experts explore these developments and try to unpack the implications for Iraq’s fragile peace and stability. Department/project Middle East and North Africa Programme, Iraq Initiative Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email Full Article
Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email
nc Breaking the Cycle of Violence: Transitional Justice for the Victims of ISIS in Syria By feedproxy.google.com Published On :: Mon, 27 Apr 2020 15:50:01 +0000 28 April 2020 This paper aims to assist the region’s local authorities, and their key foreign backers, in understanding how transitional justice can provide alternative avenues for holding local ISIS members to account while contributing to the healing of communities. Read online Download PDF Haid Haid Senior Consulting Fellow, Middle East and North Africa Programme @HaidHaid22 2020-04-28-Syria-prison.jpg A fighter with the Syrian Democratic Forces monitors prisoners accused of being affiliated with ISIS, at a prison in the northeastern Syrian city of Hassakeh on 25 October 2019. Photo: Getty Images. SummaryFollowing the territorial defeat of Islamic State of Iraq and Syria (ISIS) in northeastern Syria, the Kurdish-led autonomous administration in the region is now grappling with the task of quickly dealing with thousands of the group’s detained members while bringing justice to their victims. To that end, local authorities are focusing on the use of counterterrorism laws and courts to charge captured ISIS members and determine their guilt accordingly.The piecemeal approach to justice is deeply flawed, and raises particular concerns about due process. No precise instruments exist to determine the personal responsibility of ISIS individuals for specific crimes, or for their role in war crimes committed by the group. In any event, the scale of the crimes and the number of victims – as well as severe shortages of resources and workers – make dispensation of justice extremely difficult through the traditional legal system.Not all detained ISIS members receive prison sentences. Individuals who did not hold senior roles in the group’s apparatus and are not accused of ‘major’ crimes (in practice, largely defined as fighting for ISIS and murder) are being released under limited reconciliation deals with tribal leaders. But the involvement of local community leaders in those efforts is not enough to ensure positive results. Many victims are upset at seeing ISIS members walk free without even admitting their guilt publicly or apologizing for the pain they caused.To overcome the limitations of the current, counterterrorism-focused framework, a ‘transitional justice’ approach could provide judicial and non-judicial instruments to establish accountability for ISIS crimes and reduce community resistance to the reintegration of group members. A combination of non-judicial mechanisms such as truth commissions, missing persons’ committees, and reparations and victim-healing programmes could play a vital role in providing ISIS victims with a sense of justice while contributing to peacebuilding and stability.Ignoring the urgency of developing a long-term plan to serve justice and contribute to community healing will almost certainly allow ISIS to continue to prevent the recovery and development of northeastern Syria. This, in turn, risks undermining the stability of the country and the region at large. Department/project Middle East and North Africa Programme Full Article
nc Webinar: Breaking the Cycle of Violence: Transitional Justice for the Victims of ISIS in Syria By feedproxy.google.com Published On :: Wed, 06 May 2020 09:05:01 +0000 Research Event 12 May 2020 - 2:00pm to 3:00pmAdd to CalendariCalendar Outlook Google Yahoo Haid Haid, Senior Consulting Fellow, Middle East and North Africa Programme, Chatham HouseSara Kayyali, Syria Researcher, Middle East and North Africa Division, Human Rights WatchModerator: Lina Khatib, Director, Middle East and North Africa Programme, Chatham House You can register your interest here. Alternatively, you can watch the webinar live on the MENA Programme Facebook page.Following the territorial defeat of Islamic State of Iraq and Syria (ISIS) in northeastern Syria, the Kurdish-led autonomous administration in the region is now grappling with the task of quickly dealing with thousands of the group’s detained members while bringing justice to their victims. To that end, local authorities are focusing on the use of counterterrorism laws and courts to charge captured ISIS members and determine their guilt accordingly.In a recent research paper, author Haid Haid argues that this approach to justice is deeply flawed as it raises concerns about due process and lacks the precise instruments to determine the personal responsibility of ISIS individuals for specific crimes, or for their role in war crimes committed by the group. The paper proposes that a ‘transitional justice’ approach could provide judicial and non-judicial instruments to establish accountability for ISIS crimes and reduce community resistance to the reintegration of group members.In this webinar, part of the MENA Programme’s Online Event Series, speakers will examine the benefits of such an approach to justice for overcoming the limitations of the current, counterterrorism-focused framework. Panelists will discuss the alternative mechanisms local authorities and their key foreign backers can use to hold local ISIS members to account while contributing to the healing of communities. The event will be held on the record. Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email Department/project Middle East and North Africa Programme, Syria from Within Full Article
Reni Zhelyazkova Programme Coordinator, Middle East and North Africa Programme +44 (0)20 7314 3624 Email
nc Politics, policy-making and the presence of images of suffering children By feedproxy.google.com Published On :: Thu, 07 May 2020 08:45:52 +0000 7 May 2020 , Volume 96, Number 3 Helen Berents Read Online In 2017 Trump expressed pity for the ‘beautiful babies’ killed in a gas attack on Khan Shaykhun in Syria before launching airstrikes against President Assad's regime. Images of suffering children in world politics are often used as a synecdoche for a broader conflict or disaster. Injured, suffering, or dead; the ways in which images of children circulate in global public discourse must be critically examined to uncover the assumptions that operate in these environments. This article explores reactions to images of children by representatives and leaders of states to trace the interconnected affective and political dimensions of these images. In contrast to attending to the expected empathetic responses prompted by images of children, this article particularly focuses on when such images prompt bellicose foreign policy decision-making. In doing this, the article forwards a way of thinking about images as contentious affective objects in international relations. The ways in which images of children's bodies and suffering are strategically deployed by politicians deserves closer scrutiny to uncover the visual politics of childhood inherent in these moments of international politics and policy-making. Full Article
nc Soundscapes of war: the audio-visual performance of war by Shi'a militias in Iraq and Syria By feedproxy.google.com Published On :: Thu, 07 May 2020 09:16:54 +0000 7 May 2020 , Volume 96, Number 3 Helle Malmvig Read online This article sets out to bring sound and music to the field of visual studies in International Relations. It argues that IR largely has approached the visual field as if it was without sound; neglecting how audial landscapes frame and direct our interpretation of moving imagery. Sound and music contribute to making imagery intelligible to us, we ‘hear the pictures’ often without noticing. The audial can for instance articulate a visual absence, or blast visual signs, bring out certain emotional stages or subjects’ inner life. Audial frames steer us in distinct directions, they can mute the cries of the wounded in war, or amplify the sounds of joy of soldiers shooting in the air. To bring the audial and the visual analytically and empirically together, the article therefore proposes four key analytical themes: 1) the audial–visual frame, 2) point of view/point of audition, 3) modes of audio-visual synchronization and 4) aesthetics moods. These are applied to a study of ‘war music videos’ in Iraq and Syria made and circulated by Shi'a militias currently fighting there. Such war music videos, it is suggested, are not just artefacts of popular culture, but have become integral parts of how warfare is practiced today, and one that is shared by soldiers in the US and Europe. War music videos are performing war, just as they shape how war is known by spectators and participants alike. Full Article
nc Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 Sodium–glucose cotransport 2 inhibitors (SGLT2i) lower plasma glucose but stimulate endogenous glucose production (EGP). The current study examined the effect of dapagliflozin on EGP while clamping plasma glucose, insulin, and glucagon concentrations at their fasting level. Thirty-eight patients with type 2 diabetes received an 8-h measurement of EGP ([3-3H]-glucose) on three occasions. After a 3-h tracer equilibration, subjects received 1) dapagliflozin 10 mg (n = 26) or placebo (n = 12); 2) repeat EGP measurement with the plasma glucose concentration clamped at the fasting level; and 3) repeat EGP measurement with inhibition of insulin and glucagon secretion with somatostatin infusion and replacement of basal plasma insulin and glucagon concentrations. In study 1, the change in EGP (baseline to last hour of EGP measurement) in subjects receiving dapagliflozin was 22% greater (+0.66 ± 0.11 mg/kg/min, P < 0.05) than in subjects receiving placebo, and it was associated with a significant increase in plasma glucagon and a decrease in the plasma insulin concentration compared with placebo. Under glucose clamp conditions (study 2), the change in plasma insulin and glucagon concentrations was comparable in subjects receiving dapagliflozin and placebo, yet the difference in EGP between dapagliflozin and placebo persisted (+0.71 ± 0.13 mg/kg/min, P < 0.01). Under pancreatic clamp conditions (study 3), dapagliflozin produced an initial large decrease in EGP (8% below placebo), followed by a progressive increase in EGP that was 10.6% greater than placebo during the last hour. Collectively, these results indicate that 1) the changes in plasma insulin and glucagon concentration after SGLT2i administration are secondary to the decrease in plasma glucose concentration, and 2) the dapagliflozin-induced increase in EGP cannot be explained by the increase in plasma glucagon or decrease in plasma insulin or glucose concentrations. Full Article
nc The National Oncology PET Registry (NOPR): A monumental effort by a few leaders By jnm.snmjournals.org Published On :: 2018-01-25T14:01:12-08:00 Full Article
nc 18F-DCFPyL PET/CT Imaging in Patients with Biochemical Recurrence Prostate Cancer after Primary Local Therapy By jnm.snmjournals.org Published On :: 2019-11-01T13:36:37-07:00 Objective: To investigate the lesion detection rate of 18F-DCFPyL-PET/CT, a prostate-specific membrane antigen (PSMA) targeted PET agent, in biochemical relapse prostate cancer patients after primary local therapy. Methods: This is a prospective institutional review board-approved study of 90 patients with documented biochemical recurrence (median PSA 2.5 ng/mL, range 0.21-35.5 ng/mL) with negative conventional imaging after primary local therapies, including radical prostatectomy (n = 38), radiation (n = 27) or combination (n = 25). Patients on androgen deprivation therapy were excluded. Patients underwent whole-body 18F-DCFPyL-PET/CT (299.9±15.5 MBq) at 2 h p.i. PSMA-PET lesion detection rate was correlated with PSA, PSA kinetics and original primary tumor grade. Results: Seventy patients (77.8%) showed a positive PSMA-PET scan, identifying a total of 287 lesions: 37 prostate bed foci, 208 lymph nodes, and 42 bone/organ distant sites; 11 patients had a negative scan and 9 patients showed indeterminate lesions, which were considered negative in this study. The detection rates were 47.6% (n = 10/21), 50% (n = 5/10), 88.9% (n = 8/9), and 94% (n = 47/50) for PSA >0.2 to <0.5, 0.5 to <1.0, 1 to <2.0, and ≥2.0 ng/mL, respectively. In post-surgical patients, PSA, PSAdt and PSAvel correlated with PET results but the same was not true for post-radiation patients. These parameters also correlated with the extent of disease on PET (intrapelvic vs. extrapelvic). There was no significant difference between the rate of positive scans in patients with higher grade vs lower grade primary tumors (Gleason score ≥4+3 vs <3+4). Tumor recurrence was histology confirmed in 40% (28/70) of patients. On a per-patient basis, positive predictive value was 93.3% (95% CI, 77.6-99.2%) by histopathologic validation, and 96.2% (95% CI, 86.3-99.7%) by the combination of histology and imaging/clinical follow-up. Conclusion: 18F-DCFPyL-PET/CT imaging offers high detection rates in biochemically recurrent prostate cancer patients; and is positive in about 50% of patients with PSA <0.5 ng/mL, which could substantially impact clinical management. In post-surgical patients, 18F-DCFPyL-PET/CT correlates with PSA, PSAdt and PSAvel suggesting it may have prognostic value. 18F-DCFPyL-PET/CT is highly promising for localizing sites of recurrent prostate cancer. Full Article
nc 3-year freedom from progression following 68GaPSMA PET CT triaged management in men with biochemical recurrence post radical prostatectomy. Results of a prospective multi-center trial. By jnm.snmjournals.org Published On :: 2019-11-01T13:36:36-07:00 Background: 68Ga PSMA PET CT (PSMA) is increasingly used in men with biochemical recurrence (BCR) post radical prostatectomy (RP), but its longer term prognostic / predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for 3 year freedom from progression (FFP) in men with BCR post RP undergoing salvage radiotherapy (sRT). Methods: This prospective multi-center study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA with rising PSA following RP. Management following PSMA was recorded but not mandated. PSMA protocols were standardised across sites and reported prospectively. Clinical, pathological and surgical information, sRT, timing and duration of androgen deprivation (ADT), 3 year PSA results and clinical events were documented. FFP was defined as a PSA rise ≤ 0.2ng/mL above nadir post sRT, with no additional treatment. Results: The median PSA was 0.26ng/mL (IQR 0.15 - 0.59) and follow-up 38 months (IQR 31-43). PSMA was negative in 34.6% (90/260), confined to prostate fossa 21.5% (56/260), pelvic nodes 26.2% (68/260), and distant disease 17.7% (46/260). 71.5% (186/260) received sRT, 38.2% (71/186) to the fossa only, 49.4% (92/186) fossa + pelvic nodes and 12.4% (23/186) nodes alone/SBRT. PSMA was highly predictive of FFP at 3 years following sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative/fossa confined vs. 45% (39/86) for extra fossa disease (p<0.0001). On logistic regression PSMA was more independently predictive of FFP than established clinical predictors, including PSA, T-stage, surgical margin status or Gleason score (P < 0.002). 32% of men with a negative PSMA PET did not receive treatment. Of these, 66% (19/29) progressed, with a mean rise in PSA of 1.59ng/mL over the 3 years. Conclusion: PSMA PET result is highly predictive of FFP at 3 years in men undergoing sRT for BCR following RP. In particular, men with negative PSMA PET or disease identified as still confined to the prostate fossa demonstrate high FFP, despite receiving less extensive radiotherapy and lower rates of additional ADT than those with extra fossa disease. Full Article
nc Can fluorescence-guided surgery help identify all lesions in unknown locations or is the integrated use of a roadmap created by preoperative imaging mandatory? A blinded study in prostate cancer patients. By jnm.snmjournals.org Published On :: 2019-11-11T12:55:20-08:00 Rationale: Lymphatic tracers can help visualize the lymphatic drainage patterns and sentinel nodes of individual prostate cancer patients. To determine the role of nuclear medicine, in particular the positional guidance of a SPECT/CT-based 3D imaging roadmap, in this process we studied to which extend fluorescence-guidance underestimated the number of target lesions. Methods: SPECT/CT imaging was performed after intraprostatic tracer administration of either ICG-99mTc-nanocolloid (hybrid tracer group) or 99mTc-nanocolloid to create a roadmap that depicted all sentinel nodes (SNs). Patients who received 99mTc-nanocolloid were injected with "free" ICG immediately prior to surgery ("free" ICG group). Before unblinding, fluorescence-guidance was used for intraoperative SN identification. This was followed by extended pelvic lymph node dissection (ePLND). Following unblinding of the SPECT/CT images, the number of missed SN’s were recorded and their resection was pursued when the anatomy allowed. Results: Preoperative SPECT/CT revealed no differences in the SN identification rate between ICG-99mTc-nanocolloid and 99mTc-nanocolloid. However, fluorescence-guidance only allowed intraoperative removal of all SNs in 40% of patients in the hybrid tracer group and in 20% of patients in the "free" ICG group. Overall, 75.9% of the intraoperatively resected SNs in the hybrid tracer group and 51.8% of the SNs in the "free" ICG group were removed solely under fluorescence-guidance. During ePLND 22 additional SNs were resected (7 in the hybrid tracer group and 15 in the "free" ICG group). After unblinding 18 remaining SNs were identified (6 in the hybrid group and 12 in the "free" ICG group). In the "free" ICG group, ex vivo evaluation of the excised specimens revealed that 14 SNs removed under ePLND or after unblinding contained radioactivity but no fluorescence. Conclusion: The preoperative imaging roadmap provided by SPECT/CT enhanced the detection of prostate SNs in more ectopic locations in 17 of the 25 patients and the hybrid tracer ICG-99mTc-nanocolloid was shown to outperform "free" ICG. Overall, fluorescence-guided pelvic nodal surgery underestimated the number of SNs in 60-80% of patients. Full Article
nc Initial studies with [11C]vorozole positron emission tomography detect over-expression of intra-tumoral aromatase in breast cancer By jnm.snmjournals.org Published On :: 2019-11-22T10:43:33-08:00 Introduction: Aromatase inhibitors are the mainstay of hormonal therapy in estrogen receptor positive, postmenopausal breast cancer, although response rate is just over 50%. The goal of the present study was to validate and optimize positron emission tomography (PET) with 11C-vorozole for measuring aromatase expression in postmenopausal breast cancer. Methods: Ten newly diagnosed, postmenopausal women with biopsy confirmed breast cancer were administered 11C-vorozole intravenously and PET emission data collected between 40 – 90 minutes post-injection. Tracer injection and scanning were repeated 2 hours after ingestion of 2.5mg letrozole p.o. Mean and maximal standard uptake values and ratios to non-tumor tissue (SUVs, SUVRs) were calculated for tumor and non-tumor regions at baseline and after letrozole. Biopsy specimens from the same tumors were stained for aromatase using immunohistochemistry and evaluated for stain intensity and the percentage of immune-positive cells. Results: Seven of the 10 women (70%) demonstrated increased focal uptake of tracer (SUVR>1.1) coinciding with the mammographic location of the lesion. The other 3 women (30%) did not show increased uptake in the tumor (SUVR <1.0). All of the cases with SUVR above 1.1 had SUVs above 2.4 and there was no overlap in SUV between the two groups, with mean SUV in tumors overexpressing aromatase (SUVR>1.1) ranging from 2.47 to 13.6, while tumors not overexpressing aromatase (SUVR<1) ranged from 0.8 to 1.8. Pretreatment with letrozole reduced tracer uptake in the majority of subjects; although the %blocking varied across and within tumors. Tumors with high SUV in vivo also showed high staining intensity on IHC. Conclusion: PET with 11C-vorozole is a useful technique for measuring aromatase expression in individual breast lesions, enabling a non-invasive quantitative measurement of baseline and post-treatment aromatase availability in primary tumors and metastatic lesions. Full Article
nc 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) By jnm.snmjournals.org Published On :: 2019-11-22T10:43:33-08:00 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. Full Article
nc Long term follow-up and outcomes of re-treatment in an expanded 50 patient single-center phase II prospective trial of Lutetium-177 (177Lu) PSMA-617 theranostics in metastatic castrate-resistant prostate cancer By jnm.snmjournals.org Published On :: 2019-11-22T10:43:33-08:00 Objectives: Lutetium-177 (177Lu)-PSMA-617 (LuPSMA) is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castrate-resistant prostate cancer (mCRPC). We now report their longer-term outcomes including a 20 patient extension cohort and outcomes of subsequent systemic treatments following completion of trial therapy. Methods: 50 patients with PSMA-avid mCRPC who had progressed after standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Endpoints included PSA response (PCWG2), toxicity (CTCAE v4.03), imaging response, patient-reported health-related quality of life (QoL), progression-free and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including LuPSMA. Results: 75 men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 months) and extensive prior treatment including prior docetaxel (84%), cabazitaxel (48%), and abiraterone and/or enzalutamide (90%). The mean administered radioactivity was 7.5 GBq/cycle. PSA decline ≥ 50% was achieved in 32 of 50 patients (64%, 95% CI 50-77%), including 22 patients (44%, 95% CI 30-59%) with ≥ 80% decrease. Of 27 patients with measurable soft tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to LuPSMA were self-limiting G1-2 dry mouth (66%), transient G1-2 nausea (48%), G3-4 thrombocytopenia (10%) and G3 anemia (10%). Brief pain inventory severity and interference scores decreased at all time points including at the 3 month follow-up with a decrease of -1.2 (95% CI -0.5 to -1.9, P = 0.001) and 1.0 (95% CI -0.2 to -0.18, P = 0.013), respectively. At a median follow-up of 31.4 months, median OS was 13.3 months (95% CI 10.5-18.7) with a significantly longer survival of 18.4 months (95% CI 13.8-23.8) in patients achieving a PSA decline ≥ 50%. At progression following prior response, further LuPSMA was administered to 15 (30%) patients (median 2 cycles commencing 359 days from enrolment) with PSA decline ≥ 50% in 11 patients (73%). 4 of 21 patients (19%) receiving other systemic therapies upon progression experienced PSA decline ≥ 50%. There were no unexpected adverse events with LuPSMA re-treatment. Conclusion: This expanded 50 patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity and improved QoL with LuPSMA radioligand therapy. Upon progression, re-challenge LuPSMA demonstrated higher response rates than other systemic therapies. Full Article
nc Diagnostic value of 68Ga-PSMA PET/CT for detection of PTEN expression in prostate cancer: a pilot study By jnm.snmjournals.org Published On :: 2019-11-22T10:43:33-08:00 Purpose: To explore the value of 68Ga-PSMA-PET/CT for detection of phosphatase and tensin homolog (PTEN) - loss prostate cancer (PCa). Methods: We retrospectively enrolled 75 patients who underwent multiparametric MRI (mpMRI) and 68Ga-PSMA PET/CT before radical prostatectomy. Lesions were outlined on pathological images and regions of interest were drawn on matched mpMRI and PET/CT images. Imaging parameters including average apparent diffusion coefficient (ADCmean) and maximum standardized uptake value (SUVmax) were derived. Immunohistochemical staining was carried out to evaluate the PTEN status. The diagnostic performance of imaging parameters was analyzed by receiver operating characteristics (ROC) analysis. A univariate logistic regression analyses were used to evaluate the association between clinical and imaging variables and PTEN status. Results: Totally, 103 lesions from 54 patients were analyzed. Of these lesions, 34 of 103 (33.0%) showed PTEN-loss status. Our study showed a strong association between SUVmax and PTEN-loss tumors both in the per-patient analysis (P < 0.01) and per-lesion analysis (P < 0.01), yielding the sensitivity and specificity of 0.80 and 0.77 in the per-patient analysis and 0.83 and 0.74 in the per-lesion analysis. Meanwhile, higher pathological PSMA expression was found in the PTEN-deficiency tumors. However, there was no significant difference between PTEN-loss tumors and PTEN-intact tumors using parameters including ADCmean (P > 0.05) and PI-RADS score (P > 0.05). Surprisingly, SUVmax was a significant predictor for detection of PTEN-loss tumors (odds ratio: 7.56, 95% confidence interval: 2.18-26.24, per-patient analysis; odds ratio: 13.66, 95% confidence interval: 4.32-43.24, per-lesion analysis). Conclusion: 68Ga-PSMA-PET/CT could effectively detect aggressive PTEN-loss tumors. Full Article
nc Pre-treatment 18F-FDG PET/CT Radiomics predict local recurrence in patients treated with stereotactic radiotherapy for early-stage non-small cell lung cancer: a multicentric study By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 Purpose: The aim of this retrospective multicentric study was to develop and evaluate a prognostic FDG PET/CT radiomics signature in early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic radiotherapy (SBRT). Material and Methods: Patients from 3 different centers (n = 27, 29 and 8) were pooled to constitute the training set, whereas the patients from a fourth center (n = 23) were used as the testing set. The primary endpoint was local control (LC). The primary tumour was semi-automatically delineated in the PET images using the Fuzzy locally adaptive Bayesian algorithm, and manually in the low-dose CT images. A total of 184 IBSI-compliant radiomic features were extracted. Seven clinical and treatment parameters were included. We used ComBat to harmonize radiomic features extracted from the four institutions relying on different PET/CT scanners. In the training set, variables found significant in the univariate analysis were fed into a multivariate regression model and models were built by combining independent prognostic factors. Results: Median follow-up was 21.1 (1.7 – 63.4) and 25.5 (7.7 – 57.8) months in training and testing sets respectively. In univariate analysis, none of the clinical variables, 2 PET and 2 CT features were significantly predictive of LC. The best predictive models in the training set were obtained by combining one feature from PET, namely information correlation 2 (IC2) and one from CT (Flatness), reaching a sensitivity of 100% and a specificity of 96%. Another model combining 2 PET features (IC2 and Strength), reached sensitivity of 100% and specificity of 88%, both with an undefined hazard ratio (HR) (p<0.001). The latter model obtained an accuracy of 0.91 (sensitivity 100%, specificity 81%), with a HR undefined (P = 0.023) in the testing set, however other models relying on CT radiomics features only or the combination of PET and CT features failed to validate in the testing set. Conclusion: We showed that two radiomic features derived from FDG PET were independently associated with LC in patients with NSCLC undergoing SBRT and could be combined in an accurate predictive model. This model could provide local relapse-related information and could be helpful in clinical decision-making. Full Article
nc Differential expression of glucose transporters and hexokinases in prostate cancer with a neuroendocrine gene signature: a mechanistic perspective for FDG imaging of PSMA-suppressed tumors By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 Purpose: Although the incidence of de novo neuroendocrine prostate cancer (NEPC) is rare, recent data suggests that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine (NE) hallmarks and androgen receptor (AR)-suppression in prostate cancer (PC). Previous clinical reports indicate that PCs with a phenotype similar to NE tumors can be more amenable to imaging by 18F-Fluorodeoxyglucose (FDG) rather than PSMA-targeting radioligands. In this study, we evaluated the association between NE gene signature and FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported FDG-avidity of PSMA-suppressed tumors. Methods: Data mining approaches, cell lines and patient-derived xenograft (PDX) models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes: HK1 to 3 and GCK) and PSMA (FOLH1 gene) following AR-inhibition and in correlation with NE hallmarks. Also, we characterize a NE-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no NE histopathology. We measured glucose uptake in a NE-induced in vitro model and a zebrafish model by non-radioactive imaging of glucose uptake using fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrates that a NE gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR-inhibitors, high expression of GCK and low expression of SLC2A12 correlated with NE histopathology and PSMA gene suppression. GLUT12-suppression and amplification of glucokinase was observed in NE-induced PC cell lines and PDX models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: NE gene signature in NEPC and NELPC associates with a distinct transcriptional profile of GLUTs and HKs. PSMA-suppression correlates with GLUT12-suppression and glucokinase-amplification. Alteration of FDG uptake-associated genes correlated positively with higher glucose uptake in AR and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient pre-clinical method for monitoring non-radioactive glucose uptake. Full Article