pp Fine-Tuning Control: Pattern Management Versus Supplementation: View 1: Pattern Management: an Essential Component of Effective Insulin Management By spectrum.diabetesjournals.org Published On :: 2001-04-01 Jan PearsonApr 1, 2001; 14:Articles Full Article
pp A Novel Approach to Adolescents With Type 1 Diabetes: The Team Clinic Model By spectrum.diabetesjournals.org Published On :: 2015-02-01 Jennifer K. RaymondFeb 1, 2015; 28:68-71Care Innovations Full Article
pp From DSME to DSMS: Developing Empowerment-Based Diabetes Self-Management Support By spectrum.diabetesjournals.org Published On :: 2007-10-01 Martha Mitchell FunnellOct 1, 2007; 20:221-226Articles Full Article
pp Diabetes Self-Management Education for Older Adults: General Principles and Practical Application By spectrum.diabetesjournals.org Published On :: 2006-10-01 Emmy SuhlOct 1, 2006; 19:234-240Articles Full Article
pp A Review of Volunteer-Based Peer Support Interventions in Diabetes By spectrum.diabetesjournals.org Published On :: 2011-05-01 Tricia S. TangMay 1, 2011; 24:85-98From Research to Practice/Behavioral Interventions for Diabetes Self-Management Full Article
pp Overview of Peer Support Models to Improve Diabetes Self-Management and Clinical Outcomes By spectrum.diabetesjournals.org Published On :: 2007-10-01 Michele HeislerOct 1, 2007; 20:214-221Articles Full Article
pp The Diabetes Attitudes, Wishes, and Needs (DAWN) Program: A New Approach to Improving Outcomes of Diabetes Care By spectrum.diabetesjournals.org Published On :: 2005-07-01 Soren E. SkovlundJul 1, 2005; 18:136-142Lifestyle and Behavior Full Article
pp Happy Family: Investing for the Future By www8.gsb.columbia.edu Published On :: Tue, 07 Apr 2020 15:00:27 +0000 What strategic and operational challenges lie ahead for innovative start-up Happy Family, a leading producer of organic baby foods? Full Article
pp It felt like prison - Cruise ship worker happy to be home By jamaica-star.com Published On :: Thu, 07 May 2020 05:01:43 -0500 "It felt like prison." Those are the exact words of Jermaine who returned to the island yesterday after he was stranded on a cruise ship for 56 days in South Hampton, United Kingdom. "Bwoy we are out of prison ... it was rough mentally. They... Full Article
pp Alumni and Students From Greater China Donate PPE to NY Healthcare Workers Desperate for Gear By www8.gsb.columbia.edu Published On :: Thu, 16 Apr 2020 00:00:00 -0400 As the pandemic ebbed in China, alumni from the region raised more than $2.1 million to send crucial protective gear to New York healthcare workers. Full Article
pp State Cyber Interventions Below the Threshold of the Use of Force: Challenges in the Application of International Law By feedproxy.google.com Published On :: Wed, 17 Apr 2019 10:45:01 +0000 Invitation Only Research Event 30 April 2019 - 10:00am to 4:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Chair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House Under what circumstances will a state-sponsored cyberattack on another state that falls below the threshold of the use of force be a breach of international law – for example, hacking into another state’s electoral databases, usurping inherently governmental functions such as parliamentary processes or an attack on another state’s financial system? In the dynamic field of state cyber operations, persistent, low-level cyberattacks are increasing, as are multilateral attempts to attribute the attacks to the states responsible. There is general agreement that international law applies to cyberspace but the question is how it applies and with what consequences. This meeting will bring together a small group of academics and practitioners to explore the application of international law to states’ cyber operations that interfere in the internal affairs of another state and which fall below the threshold of the use of force. What is the law on non-intervention in international law and how does it apply to states’ cyber activities? Does the Nicaragua case represent the best expression of the law in this area including the requirement of coercion? And are there any other principles of international law that are relevant? The meeting will also consider processes and procedures for agreeing on the law and best practices. The purpose of the meeting will be to inform a research paper by Chatham House. Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project International Law Programme Full Article
pp Cyber Interference in Elections: Applying a Human Rights Framework By feedproxy.google.com Published On :: Thu, 25 Apr 2019 13:55:01 +0000 Invitation Only Research Event 7 May 2019 - 10:00am to 4:15pm Chatham House | 10 St James's Square | London | SW1Y 4LE The use of social media, including algorithms, bots and micro-targeted advertising, has developed rapidly while there has been a policy lag in identifying and addressing the challenges posed to democracy by the manipulation of voters through cyber activity. What role should international human rights law play in developing a normative framework to address potential harms caused by such cyber activity including the closing down of democratic space, the spread of disinformation and hate speech? This meeting will bring together a small group of academics and practitioners to explore the implications of applying a human rights framework to both the activities of social media companies and the activities of governments and international organizations in seeking to regulate their activity. The purpose of the meeting will be to inform a report that will provide an overview of the applicable law and recommendations for how that law might inform future policy and regulation. Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project International Law Programme, Rights, Accountability and Justice Full Article
pp Tackling Cyber Disinformation in Elections: Applying International Human Rights Law By feedproxy.google.com Published On :: Wed, 18 Sep 2019 10:30:02 +0000 Research Event Tackling Cyber Disinformation in Elections: Applying International Human Rights Law 6 November 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Susie Alegre, Barrister and Associate Tenant, Doughty Street ChambersEvelyn Aswad, Professor of Law and the Herman G. Kaiser Chair in International Law, University of OklahomaBarbora Bukovská, Senior Director for Law and Policy, Article 19Kate Jones, Director, Diplomatic Studies Programme, University of OxfordChair: Harriet Moynihan, Associate Fellow, International Law Programme, Chatham House Register Interest Cyber operations are increasingly used by political parties, their supporters and foreign states to influence electorates – from algorithms promoting specific messages to micro-targeting based on personal data and the creation of filter bubbles. The risks of digital tools spreading disinformation and polarizing debate, as opposed to deepening democratic engagement, have been highlighted by concerns over cyber interference in the UK’s Brexit referendum, the 2016 US presidential elections and in Ukraine. While some governments are adopting legislation in an attempt to address some of these issues, for example Germany’s ‘NetzDG’ law and France’s ‘Law against the manipulation of information’, other countries have proposed an independent regulator as in the case of the UK’s Online Harms white paper. Meanwhile, the digital platforms, as the curators of content, are under increasing pressure to take their own measures to address data mining and manipulation in the context of elections. How do international human rights standards, for example on freedom of thought, expression and privacy, guide the use of digital technology in the electoral context? What practical steps can governments and technology actors take to ensure policies, laws and practices are in line with these fundamental standards? And with a general election looming in the UK, will these steps come soon enough? This event brings together a wide range of stakeholders including civil society, the tech sector, legal experts and government, coincides with the publication of a Chatham House research paper on disinformation, elections and the human rights framework. Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Department/project International Law Programme, Cyber, Sovereignty and Human Rights, Rights, Accountability and Justice Full Article
pp Sovereignty and Non-Intervention: The Application of International Law to State Cyberattacks By feedproxy.google.com Published On :: Fri, 01 Nov 2019 10:55:01 +0000 Research Event 4 December 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Douglas, Legal Director, GCHQZhixiong Huang, Luojia Chair of International Law, Wuhan UniversityNemanja Malisevic, Director of Digital Diplomacy, MicrosoftHarriet Moynihan, Associate Fellow, International Law Programme, Chatham HouseChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House International law applies to cyber operations – but views differ on exactly how. Does state-sponsored interference in another state's affairs using cyber means – for example, disinformation campaigns in elections, disabling government websites, or disrupting transport systems – breach international law? If so, on what basis and how are the principles of sovereignty and non-intervention relevant? States are increasingly attributing cyber operations to other states and engaging in the debate on how international law applies, including circumstances that would justify countermeasures.As states meet to debate these issues at the UN, the panel will explore how international law regulates cyberoperations by states, consider the prospects of progress at the UN, and assess the value of other initiatives.This event coincides with the launch of a Chatham House research paper which analyses how the principles of sovereignty and intervention apply in the context of cyberoperations, and considers a way forward for agreeing a common understanding of cyber norms.This event will bring together a broad group of actors, including policymakers, the private sector, legal experts and civil society, and will be followed by a drinks reception. Department/project International Law Programme, Cyber, Sovereignty and Human Rights Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Full Article
pp Online Disinformation and Political Discourse: Applying a Human Rights Framework By feedproxy.google.com Published On :: Tue, 05 Nov 2019 11:03:02 +0000 6 November 2019 Although some digital platforms now have an impact on more people’s lives than does any one state authority, the international community has been slow to hold to account these platforms’ activities by reference to human rights law. This paper examines how human rights frameworks should guide digital technology. Download PDF Kate Jones Associate Fellow, International Law Programme @katejones77 LinkedIn 2019-11-05-Disinformation.jpg A man votes in Manhattan, New York City, during the US elections on 8 November 2016. Photo: Getty Images. SummaryOnline political campaigning techniques are distorting our democratic political processes. These techniques include the creation of disinformation and divisive content; exploiting digital platforms’ algorithms, and using bots, cyborgs and fake accounts to distribute this content; maximizing influence through harnessing emotional responses such as anger and disgust; and micro-targeting on the basis of collated personal data and sophisticated psychological profiling techniques. Some state authorities distort political debate by restricting, filtering, shutting down or censoring online networks.Such techniques have outpaced regulatory initiatives and, save in egregious cases such as shutdown of networks, there is no international consensus on how they should be tackled. Digital platforms, driven by their commercial impetus to encourage users to spend as long as possible on them and to attract advertisers, may provide an environment conducive to manipulative techniques.International human rights law, with its careful calibrations designed to protect individuals from abuse of power by authority, provides a normative framework that should underpin responses to online disinformation and distortion of political debate. Contrary to popular view, it does not entail that there should be no control of the online environment; rather, controls should balance the interests at stake appropriately.The rights to freedom of thought and opinion are critical to delimiting the appropriate boundary between legitimate influence and illegitimate manipulation. When digital platforms exploit decision-making biases in prioritizing bad news and divisive, emotion-arousing information, they may be breaching these rights. States and digital platforms should consider structural changes to digital platforms to ensure that methods of online political discourse respect personal agency and prevent the use of sophisticated manipulative techniques.The right to privacy includes a right to choose not to divulge your personal information, and a right to opt out of trading in and profiling on the basis of your personal data. Current practices in collecting, trading and using extensive personal data to ‘micro-target’ voters without their knowledge are not consistent with this right. Significant changes are needed.Data protection laws should be implemented robustly, and should not legitimate extensive harvesting of personal data on the basis of either notional ‘consent’ or the data handler’s commercial interests. The right to privacy should be embedded in technological design (such as by allowing the user to access all information held on them at the click of a button); and political parties should be transparent in their collection and use of personal data, and in their targeting of messages. Arguably, the value of personal data should be shared with the individuals from whom it derives.The rules on the boundaries of permissible content online should be set by states, and should be consistent with the right to freedom of expression. Digital platforms have had to rapidly develop policies on retention or removal of content, but those policies do not necessarily reflect the right to freedom of expression, and platforms are currently not well placed to take account of the public interest. Platforms should be far more transparent in their content regulation policies and decision-making, and should develop frameworks enabling efficient, fair, consistent internal complaints and content monitoring processes. Expertise on international human rights law should be integral to their systems.The right to participate in public affairs and to vote includes the right to engage in public debate. States and digital platforms should ensure an environment in which all can participate in debate online and are not discouraged from standing for election, from participating or from voting by online threats or abuse. Department/project International Law Programme, Cyber, Sovereignty and Human Rights, Rights, Accountability and Justice Full Article
pp The Application of International Law to State Cyberattacks: Sovereignty and Non-Intervention By feedproxy.google.com Published On :: Fri, 29 Nov 2019 16:56:12 +0000 2 December 2019 Hostile cyber operations by one state against another state are increasingly common. This paper analyzes the application of the sovereignty and non-intervention principles in relation to states’ cyber operations in another state below the threshold of the use of force. Read online Download PDF Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 2019-11-29-Intl-Law-Cyberattacks.jpg A computer hacked by a virus known as Petya. The Petya ransomware cyberattack hit computers of Russian and Ukrainian companies on 27 June 2017. Photo: Getty Images. SummaryThe vast majority of state-to-state cyberattacks consist of persistent, low-level intrusions that take place below the threshold of use of force. International law, including the principle of non-intervention in another state’s internal affairs and the principle of sovereignty, applies to these cyber operations.It is not clear whether any unauthorized cyber intrusion would violate the target state’s sovereignty, or whether there is a threshold in operation. While some would like to set limits by reference to effects of the cyber activity, at this time such limits are not reflected in customary international law. The assessment of whether sovereignty has been violated therefore has to be made on a case by case basis, if no other more specific rules of international law apply.In due course, further state practice and opinio iuris may give rise to an emerging cyber-specific understanding of sovereignty, just as specific rules deriving from the sovereignty principle have crystallized in other areas of international law.Before a principle of due diligence can be invoked in the cyber context, further work is needed by states to agree upon rules as to what might be expected of a state in this context.The principle of non-intervention applies to a state’s cyber operations as it does to other state activities. It consists of coercive behaviour by one state that deprives the target state of its free will in relation to the exercise of its sovereign functions in order to compel an outcome in, or conduct with respect to, a matter reserved to the target state.In practice, activities that contravene the non-intervention principle and activities that violates sovereignty will often overlap.In order to reach agreement on how international law applies to states’ cyber operations below the level of use of force, states should put their views on record, where possible giving examples of when they consider that an obligation may be breached, as states such as the UK, Australia, France and the Netherlands have done.Further discussion between states should focus on how the rules apply to practical examples of state-sponsored cyber operations. There is likely to be more commonality about specific applications of the law than there is about abstract principles.The prospects of a general treaty in this area are still far off. In due course, there may be benefit in considering limited rules, for example on due diligence and a prohibition on attacking critical infrastructure, before tackling broad principles. Department/project International Law Programme, Cyber, Sovereignty and Human Rights Full Article
pp POSTPONED: Supporting Civic Space: The Role and Impact of the Private Sector By feedproxy.google.com Published On :: Wed, 22 Jan 2020 17:05:01 +0000 Invitation Only Research Event 16 March 2020 - 11:00am to 5:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE A healthy civic space is vital for an enabling business environment. In recognition of this, a growing number of private sector actors are challenging, publicly or otherwise, the deteriorating environment for civic freedoms.However, this corporate activism is often limited and largely ad hoc. It remains confined to a small cluster of multinationals leaving potential routes for effective coordination and collaboration with other actors underexplored.This roundtable will bring together a diverse and international group of business actors, civil society actors and foreign policy experts to exchange perspectives and experiences on how the private sector can be involved in issues around civic space. The meeting will provide an opportunity to explore the drivers of – and barriers to – corporate activism, develop a better understanding of existing initiatives, identify good practice and discuss practical strategies for the business community.This meeting will be the first of a series of roundtables at Chatham House in support of initiatives to build broad alliances for the protection of civic space. Attendance at this event is by invitation only. PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. Department/project International Law Programme, Global Governance and the Rule of Law, Rights, Accountability and Justice Jacqueline Rowe Programme Assistant, International Law Programme 020 7389 3287 Email Full Article
pp 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
pp Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome By feedproxy.google.com Published On :: 2020-04-01 Xien Yu ChuaApr 1, 2020; 19:730-743Technological Innovation and Resources Full Article
pp 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
pp A cross-linking mass spectrometry approach defines protein interactions in yeast mitochondria By feedproxy.google.com Published On :: 2020-04-24 Andreas LindenApr 24, 2020; 0:RA120.002028v1-mcp.RA120.002028Research Full Article
pp Proximity Dependent Biotinylation: Key Enzymes and Adaptation to Proteomics Approaches By feedproxy.google.com Published On :: 2020-05-01 Payman Samavarchi-TehraniMay 1, 2020; 19:757-773Review Full Article
pp 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
pp European Approaches to Remote Warfare By feedproxy.google.com Published On :: Fri, 26 Apr 2019 14:50:01 +0000 Research Event 15 May 2019 - 9:00am to 6:00pm Brussels, Belgium With continuing instability at Europe's borders, along with uncertainty on future US support for NATO, many European countries are increasing their allocations to defence budgets and to collective European strategic defence. In addition, with non-state armed groups creating instability and threatening civilian lives and livelihoods in proximity to the EU’s borders, various operations have been carried out in conflict theatres in the Middle East, North Africa and the Sahel under the auspices of NATO, the UN, the EU or by single EU member states.Although European military personnel have been deployed in many regions, with countries becoming more reluctant to deploy ‘boots on the ground’, warfare has been increasingly conducted through remote means. This has led to criticism on the limited transparency and accountability mechanisms at work in these operations, while some have questioned the military effectiveness of such tactics or the capacity and willingness of states to ensure that targets are struck accurately and without impact on civilian populations.Against this background, the EU has started allocating resources to military research and development projects with a focus on unmanned systems and related technologies. Under the auspices of the European Defence Fund such funding is set to increase, while potential bilateral programmes between some states have also been explored. Despite concerns raised by the European Parliament, the development of these policies and technologies has taken place without significant consideration of what the legal, ethical and military-strategic impact of these instruments might be. This event will bring together a range of experts, policymakers and civil society organizations to discuss the technology horizon of European defence investments and policy developments around remote warfare. Participants will discuss the implications of the new EU defence fund, legal, ethical, and transparency issues in military research and development and the position of the EU as a global actor. This event is being organized in partnership with PAX Netherlands.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Department/project International Security Programme Nilza Amaral Project Manager, International Security Programme Email Full Article
pp 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
pp The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace By feedproxy.google.com Published On :: Tue, 11 Feb 2020 10:55:01 +0000 Invitation Only Research Event 12 May 2020 - 10:00am to 11:30amAdd to CalendariCalendar Outlook Google Yahoo Smart Peace brings together global expertise in conflict analysis and research, peacebuilding and mediation programming, and behavioural science and evaluation. Together, Smart Peace partners are developing integrated and adaptive peace initiatives, working with local partners to prevent and resolve complex and intractable conflicts in Central African Republic, Myanmar and northern Nigeria. This roundtable is an opportunity for Smart Peace partners to share the Smart Peace concept, approach and objectives, and experiences of the first phases of programme implementation. Roundtable discussions among participants from policy, practice and research communities will inform future priorities and planning for Smart Peace learning, advocacy and communication. Smart Peace partners include Conciliation Resources, Behavioural Insights Team, The Centre for Humanitarian Dialogue, Chatham House, ETH Zurich, International Crisis Group and The Asia Foundation. Nilza Amaral Project Manager, International Security Programme Email Department/project International Security Programme, Smart Peace Full Article
pp 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
pp Nuclear Weapons: Innovative Approaches for the Complex International Security Environment By feedproxy.google.com Published On :: Fri, 28 Feb 2020 10:09:26 +0000 This programme of work addresses the conundrum of nuclear weapons as a wicked problem in a complex adaptive system. Understanding the complexity and the wickedness of the situation allows analysts and strategic planners to approach these complex and intractable issues in new and transformative ways – with a better chance of coping or succeeding and reducing the divisions between experts.Using complexity theory, a complex adaptive system representing the international system and its interaction with the environment can be represented through an interactive visualization tool that will aid thought processes and policy decision-making. Until recently, analysts did not have the tools to be able to create models that could represent the complexity of the international system and the role that nuclear weapons play. Now that these tools are available, analysts should use them to enable decision-makers to gain insights into the range of possible outcomes from a set of possible actions.This programme builds on work by Chatham House on cyber security and artificial intelligence (AI) in the nuclear/strategic realms.In order to approach nuclear weapons as wicked problems in a complex adaptive system from different and sometimes competing perspectives, the programme of work involves the wider community of specialists who do not agree on what constitutes the problems of nuclear weapons nor on what are the desired solutions.Different theories of deterrence, restraint and disarmament are tested. The initiative is international and inclusive, paying attention to gender, age and other aspects of diversity, and the network of MacArthur Grantees are given the opportunity to participate in the research, including in the writing of research papers, so that the complexity modelling can be tested against a wide range of approaches and hypotheses.In addition, a Senior Reference Group will work alongside the programme, challenging its outcome and findings, and evaluating and guiding the direction of the research.This project is supported by the MacArthur Foundation. Full Article
pp Supporting NHS Cybersecurity During COVID-19 is Vital By feedproxy.google.com Published On :: Thu, 02 Apr 2020 12:09:33 +0000 2 April 2020 Joyce Hakmeh Senior Research Fellow, International Security Programme; Co-Editor, Journal of Cyber Policy @joycehakmeh LinkedIn The current crisis is an opportunity for the UK government to show agility in how it deals with cyber threats and how it cooperates with the private sector in creating cyber resilience. 2020-04-02-NHS-nurse-tech-cyber Nurse uses a wireless electronic tablet to order medicines from the pharmacy at The Queen Elizabeth Hospital, Birmingham, England. Photo by Christopher Furlong/Getty Images. The World Health Organization, US Department of Health and Human Services, and hospitals in Spain, France and the Czech Republic have all suffered cyberattacks during the ongoing COVID-19 crisis.In the Czech Republic, a successful attack targeted a hospital with one of the country’s biggest COVID-19 testing laboratories, forcing its entire IT network to shut down, urgent surgical operations to be rescheduled, and patients to be moved to nearby hospitals. The attack also delayed dozens of COVID-19 test results and affected the hospital’s data transfer and storage, affecting the healthcare the hospital could provide.In the UK, the National Health Service (NHS) is already in crisis mode, focused on providing beds and ventilators to respond to one of the largest peacetime threats ever faced. But supporting the health sector goes beyond increasing human resources and equipment capacity.Health services ill-preparedCybersecurity support, both at organizational and individual level, is critical so health professionals can carry on saving lives, safely and securely. Yet this support is currently missing and the health services may be ill-prepared to deal with the aftermath of potential cyberattacks.When the NHS was hit by the Wannacry ransomware attack in 2017 - one of the largest cyberattacks the UK has witnessed to date – it caused massive disruption, with at least 80 of the 236 trusts across England affected and thousands of appointments and operations cancelled. Fortunately, a ‘kill-switch’ activated by a cybersecurity researcher quickly brought it to a halt.But the UK’s National Cyber Security Centre (NCSC), has been warning for some time against a cyber attack targeting national critical infrastructure sectors, including the health sector. A similar attack, known as category one (C1) attack, could cripple the UK with devastating consequences. It could happen and we should be prepared.Although the NHS has taken measures since Wannacry to improve cybersecurity, its enormous IT networks, legacy equipment and the overlap between the operational and information technology (OT/IT) does mean mitigating current potential threats are beyond its ability.And the threats have radically increased. More NHS staff with access to critical systems and patient health records are increasingly working remotely. The NHS has also extended its physical presence with new premises, such as the Nightingale hospital, potentially the largest temporary hospital in the world.Radical change frequently means proper cybersecurity protocols are not put in place. Even existing cybersecurity processes had to be side-stepped because of the outbreak, such as the decision by NHS Digital to delay its annual cybersecurity audit until September. During this audit, health and care organizations submit data security and protection toolkits to regulators setting out their cybersecurity and cyber resilience levels.The decision to delay was made to allow the NHS organizations to focus capacity on responding to COVID-19, but cybersecurity was highlighted as a high risk, and the importance of NHS and Social Care remaining resilient to cyberattacks was stressed.The NHS is stretched to breaking point. Expecting it to be on top of its cybersecurity during these exceptionally challenging times is unrealistic, and could actually add to the existing risk.Now is the time where new partnerships and support models should be emerging to support the NHS and help build its resilience. Now is the time where innovative public-private partnerships on cybersecurity should be formed.Similar to the economic package from the UK chancellor and innovative thinking on ventilator production, the government should oversee a scheme calling on the large cybersecurity capacity within the private sector to step in and assist the NHS. This support can be delivered in many different ways, but it must be mobilized swiftly.The NCSC for instance has led the formation of the Cyber Security Information Sharing Partnership (CiSP)— a joint industry and UK government initiative to exchange cyber threat information confidentially in real time with the aim of reducing the impact of cyberattacks on UK businesses.CiSP comprises organizations vetted by NCSC which go through a membership process before being able to join. These members could conduct cybersecurity assessment and penetration testing for NHS organizations, retrospectively assisting in implementing key security controls which may have been overlooked.They can also help by making sure NHS remote access systems are fully patched and advising on sensible security systems and approved solutions. They can identify critical OT and legacy systems and advise on their security.The NCSC should continue working with the NHS to enhance provision of public comprehensive guidance on cyber defence and response to potential attack. This would show they are on top of the situation, projecting confidence and reassurance.It is often said in every crisis lies an opportunity. This is an opportunity for the UK government to show agility in how it deals with cyber threats and how it cooperates with the private sector in creating cyber resilience.It is an opportunity to lead a much-needed cultural change showing cybersecurity should never be an afterthought. Full Article
pp Can Protest Movements in the MENA Region Turn COVID-19 Into an Opportunity for Change? By feedproxy.google.com Published On :: Tue, 28 Apr 2020 14:07:38 +0000 29 April 2020 Dr Georges Fahmi Associate Fellow, Middle East and North Africa Programme @GeorgesFahmi The COVID-19 pandemic will not in itself result in political change in the MENA region, that depends on the ability of both governments and protest movements to capitalize on this moment. After all, crises do not change the world - people do. 2020-04-28-covid-19-protest-movement-mena.jpg An aerial view shows the Lebanese capital Beirut's Martyrs Square that was until recent months the gathering place of anti-government demonstrators, almost deserted during the novel coronavirus crisis, on 26 March 2020. Photo by -/AFP via Getty Images. COVID-19 has offered regimes in the region the opportunity to end popular protest. The squares of Algiers, Baghdad, and Beirut – all packed with protesters over the past few months – are now empty due to the pandemic, and political gatherings have also been suspended. In Algeria, Iraq and Lebanon, COVID-19 has achieved what snipers, pro-regime propaganda, and even the economic crisis, could not.Moreover, political regimes have taken advantage of the crisis to expand their control over the political sphere by arresting their opponents, such as in Algeria where the authorities have cracked down on a number of active voices of the Hirak movement. Similarly, in Lebanon, security forces have used the pandemic as an excuse to crush sit-ins held in Martyr’s Square in Beirut and Nour Square in Tripoli.However, despite the challenges that the pandemic has brought, it also offers opportunities for protest movements in the region. While the crisis has put an end to popular mobilization in the streets, it has created new forms of activism in the shape of solidarity initiatives to help those affected by its consequences.In Iraq, for example, protest groups have directed their work towards awareness-raising and sharing essential food to help mitigate the problem of food shortages and rising prices across the country. In Algeria, Hirak activists have run online campaigns to raise awareness about the virus and have encouraged people to stay at home. Others have been cleaning and disinfecting public spaces. These initiatives increase the legitimacy of the protest movement, and if coupled with political messages, could offer these movements an important chance to expand their base of popular support.Exposes economic vulnerabilityEconomic grievances, corruption and poor provision of public services have been among the main concerns of this recent wave of protests. This pandemic only further exposes the levels of economic vulnerability in the region. COVID-19 is laying bare the socio-economic inequalities in MENA countries; this is particularly evident in the numbers of people engaged in the informal economy with no access to social security, including health insurance and pensions.Informal employment, approximately calculated by the share of the labour force not contributing to social security, is estimated to amount to 65.5% of total employment in Lebanon, 64.4% in Iraq, and 63.3% in Algeria. The crisis has underscored the vulnerability of this large percentage of the labour force who have been unable to afford the economic repercussions of following state orders to stay at home.The situation has also called attention to the vital need for efficient public services and healthcare systems. According to the fifth wave of the Arab Barometer, 74.4% of people in Lebanon are dissatisfied with their country’s healthcare services, as are 67.8% of people in Algeria and 66.5% in Iraq.Meanwhile, 66.2% of people in Lebanon believe it is necessary to pay a bribe in order to receive better healthcare, as do 56.2% of people in Iraq and 55.9% in Algeria. The COVID-19 crisis has highlighted the need for more government investment in public healthcare systems to render them more efficient and less corrupt, strengthening the protesters’ case for the need for radical socio-economic reforms.On the geopolitical level, the crisis puts into question the stability-focused approach of Western powers towards the region. For years, Western powers have directed their aid towards security forces in the interests of combating terrorism but COVID-19 has proved itself to be a much more lethal challenge to both the region and the West.Facing this new challenge requires international actors to reconsider their approach to include supporting health and education initiatives, as well as freedom of expression and transparency. As argued by Western policymakers themselves, it was China’s lack of transparency and slow response that enabled the proliferation of the virus, when it could have been contained in Wuhan back in December 2019.This crisis therefore offers regional protest movements the opportunity to capitalize on this moment and push back against the policies of Western powers that have invested in regional stability only to the extent of combating Islamic jihad. But crises do not change the world, people do. The COVID-19 pandemic will not in itself result in political change in the MENA region. Rather, it brings opportunities and risks that, when exploited, will allow political actors to advance their own agendas. While the crisis has put an end to popular mobilization and allowed regimes to tighten their grip over the political sphere, behind these challenges lie real opportunities for protest movements.The current situation represents a possibility for them to expand their popular base through solidarity initiatives and has exposed more widely the importance of addressing socio-economic inequalities. Finally, it offers the chance to challenge the stability-focused approach of Western powers towards the region which until now has predominantly focused on combating terrorism. Full Article
pp 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
pp Mapping prostate cancer lesions pre/post unsuccessful salvage lymph node dissection using repeat PSMA-PET By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 Introduction: The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with PSA persistence following salvage lymph node dissection (SLND) and pre/post procedure prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET). Material and Methods: 16 patients were included in this multicenter study. Inclusion criteria were: a) PSMA-PET performed for biochemical recurrence before SLND (pre-SLND PET) and b) repeat PSMA-PET performed for persistently elevated PSA level (≥0.1 ng/mL) ≥6 weeks after SLND (post-SLND PET). Image analysis was performed by three independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scan or PSA response after focal therapy. Results: post-SLND PET identified PCa-lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (IQR, 0.6-2.8 ng/mL). Disease was confined to the pelvis in 56% of patients (9/16) and most of these men had common iliac (6/16, 38%) and internal iliac lymph node metastases (6/16, 38%). Extrapelvic disease was detected in 31% of patients (5/16). In pre- and post-SLND PET comparison, 10/16 had at least one lesion already detected at baseline (63% PET persistence); 4/16 had new lesions only (25% PET recurrence); 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true positive. 9/14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). Conclusion: SLND of pelvic nodal metastases was often not complete according to PSMA-PET. About two thirds of patients had PET positive nodal disease after SLND already seen on pre-SLND PSMA-PET. Notably, about one quarter of patients had new lesions, not detected by pre-surgical PSMA-PET. Full Article
pp 18F-Fluorodeoxyglucose Positron Emission Tomography / Computed Tomography in Left-Ventricular Assist Device Infection: Initial Results Supporting the Usefulness of Image-Guided Therapy By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 Background: Accurate definition of the extent and severity of left-ventricular assist device (LVAD) infection may facilitate therapeutic decision making and targeted surgical intervention. Here, we explore the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for guidance of patient management. Methods: Fifty-seven LVAD-carrying patients received 85 whole-body 18F-FDG PET/CT scans for the work-up of device infection. Clinical follow-up was obtained over a period of up to two years. Results: PET/CT showed various patterns of infectious involvement of the 4 LVAD components: driveline entry point (77% of cases), subcutaneous driveline path (87%), pump pocket (49%) and outflow tract (58%). Driveline smears revealed staphylococcus or pseudomonas strains as the underlying pathogen in a majority of cases (48 and 34%, respectively). At receiver-operating characteristics analysis, an 18F-FDG standardized uptake value (SUV) >2.5 was most accurate to identify smear-positive driveline infection. Infection of 3 or all 4 LVAD components showed a trend towards lower survival vs infection of 2 or less components (P = 0.089), while involvement of thoracic lymph nodes was significantly associated with adverse outcome (P = 0.001 for nodal SUV above vs below median). Finally, patients that underwent early surgical revision within 3 months after PET/CT (n = 21) required significantly less inpatient hospital care during follow-up when compared to those receiving delayed surgical revision (n = 11; p<0.05). Conclusion: Whole-body 18F-FDG PET/CT identifies the extent of LVAD infection and predicts adverse outcome. Initial experience suggests that early image-guided surgical intervention may facilitate a less complicated subsequent course. Full Article
pp Positron lymphography via intracervical 18F-FDG injection for pre-surgical lymphatic mapping in cervical and endometrial malignancies By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Rationale: The presence of metastasis in local lymph nodes (LNs) is a key factor influencing choice of therapy and prognosis in cervical and endometrial cancers; therefore, the exploration of sentinel LNs (SLNs) is highly important. Currently, however, SLN mapping requires LN biopsy for pathologic evaluation, since there are no clinical imaging approaches that can identify tumor-positive LNs in early stages. Staging lymphadenectomy poses risks, such as leg lymphedema or lymphocyst formation. Furthermore, in 80% to 90% of patients, the explored LNs are ultimately tumor free, meaning the vast majority of patients are unnecessarily subjected to lymphadenectomy. Methods: Current lymphoscintigraphy methods only identify the anatomic location of the SLNs but do not provide information on their tumor status. There are no non-invasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, where 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is injected interstitially into the uterine cervix the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic positron emission tomography/computed tomography (PET/CT). We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all LNs (including one with a focus of only 80 tumor cells) were identified by PLG except one node with an 11-mm micrometastasis. There were 2 (10%) false-positive cases with PLG, in which final pathology of the corresponding SLNs was negative for tumor. Methods: Current lymphoscintigraphy methods only identify the anatomic location of the SLNs but do not provide information on their tumor status. There are no non-invasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, where 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is injected interstitially into the uterine cervix the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic positron emission tomography/computed tomography (PET/CT). We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all LNs (including one with a focus of only 80 tumor cells) were identified by PLG, except for one node with an 11-mm micrometastasis. There were 2 (10%) false-positive cases with PLG, in which final pathology of the corresponding SLNs was negative for tumor. Conclusion: This first-in-human study of PLG in women with uterine and cervical cancer demonstrates its feasibility and its ability to identify patients with nodal metastases, and warrants further evaluation in additional studies. Full Article
pp 11C-(+)-PHNO Trapping Reversibility for Quantitative PET Imaging of Beta-Cell-Mass in Patients with Type-1 Diabetes By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Full Article
pp Individual mapping of innate immune cell activation is a candidate marker of patient-specific trajectories of disability worsening in Multiple Sclerosis By jnm.snmjournals.org Published On :: 2020-01-31T13:36:41-08:00 Objective: To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18F-DPA-714 translocator protein (TSPO) positron emission tomography (PET), and to explore the relationship between these maps and individual trajectories of disability worsening in patients with multiple sclerosis (MS). Methods: Patients with MS (n = 37), whose trajectories of disability worsening over the 2 years preceding study entry were calculated, and healthy controls (n = 19) underwent magnetic resonance magnetic and 18F-DPA-714 PET. A threshold of significant activation of 18F-DPA-714 binding was calculated with a voxel-wise randomized permutation-based comparison between patients and controls, and used to classify each WM voxel in patients as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were employed to calculate the extent of activation in WM regions-of-interests and to classify each WM lesion as "DPA-active", "DPA-inactive" or "unclassified". Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM, (NAWM in patients=24.9±9.7%; WM in controls=14.0±7.8%, p<0.001). In patients with MS, the percentage of DPA+ voxels showed a significant increase from NAWM, to perilesional areas, T2 hyperintense lesions and T1 hypointense lesions (38.1±13.5%, 45.0±17.9%, and 51.9±22.9%, respectively, p<0.001). Among the 1379 T2 lesions identified, 512 were defined as DPA-active and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (OR=1.13, P = 0.009), a higher percentage of DPA+ voxels in the NAWM (OR=1.16, P = 0.009) and in T1-spin-echo lesions (OR=1.06, P = 0.036), were significantly associated with a retrospective more severe clinical trajectory in patients with MS. Conclusion: A more severe trajectory of disability worsening in MS is associated with an innate immune cells activation inside and around WM lesions. 18F-DPA-714 PET may provide a promising biomarker to identify patients at risk of severe clinical trajectory. Full Article
pp Kinetic modeling and test-retest reproducibility of 11C-EKAP and 11C-FEKAP, novel agonist radiotracers for PET imaging of the kappa opioid receptor in humans By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 The kappa opioid receptor (KOR) is implicated in various neuropsychiatric disorders. We previously evaluated an agonist tracer, 11C-GR103545, for PET imaging of KOR in humans. Although 11C-GR103545 showed high brain uptake, good binding specificity, and selectivity to KOR, it displayed slow kinetics and relatively large test-retest variability (TRV) of distribution volume (VT) estimates (15%). Therefore we set out to develop two novel KOR agonist radiotracers, 11C-EKAP and 11C-FEKAP, and in nonhuman primates, both tracers exhibited faster kinetics and comparable binding parameters to 11C-GR103545. The aim of this study was to assess their kinetic and binding properties in humans. Methods: Six healthy subjects underwent 120-min test-retest PET scans with both 11C-EKAP and 11C-FEKAP. Metabolite-corrected arterial input functions were measured. Regional time-activity curves (TACs) were generated for 14 regions of interest. One- and two-tissue compartment models (1TC, 2TC) and the multilinear analysis-1 (MA1) method were applied to the regional TACs to calculate VT. Time-stability of VT values and test-retest reproducibility were evaluated. Levels of specific binding, as measured by the non-displaceable binding potential (BPND) for the three tracers (11C-EKAP, 11C-FEKAP and 11C-GR103545), were compared using a graphical method. Results: For both tracers, regional TACs were fitted well with the 2TC model and MA1 method (t*=20min), but not with the 1TC model. Given unreliably estimated parameters in several fits with the 2TC model and a good match between VT values from MA1 and 2TC, MA1 was chosen as the appropriate model for both tracers. Mean MA1 VT values were highest for 11C-GR103545, followed by 11C-EKAP, then 11C-FEKAP. Minimum scan time for stable VT measurement was 90 and 110min for 11C-EKAP and 11C-FEKAP, respectively, compared with 140min for 11C-GR103545. The mean absolute TRV in MA1 VT estimates was 7% and 18% for 11C-EKAP and 11C-FEKAP, respectively. BPND levels were similar for 11C-FEKAP and 11C-GR103545, but ~25% lower for 11C-EKAP. Conclusion: The two novel KOR agonist tracers showed faster tissue kinetics than 11C-GR103545. Even with slightly lower BPND, 11C-EKAP is judged to be a better tracer for imaging and quantification of KOR in humans, based on the shorter minimum scan time and excellent test-retest. Full Article
pp Yttrium-90 Radioembolization: Telemedicine during COVID-19 outbreak, opportunity for prime time. By jnm.snmjournals.org Published On :: 2020-04-24T14:33:41-07:00 Full Article
pp Africa’s Long-standing Leaders Are Disappearing By feedproxy.google.com Published On :: Fri, 03 Jan 2020 16:07:49 +0000 3 January 2020 Dr Alex Vines OBE Managing Director, Ethics, Risk & Resilience; Director, Africa Programme Leaders who cling to power are being pushed out across the continent, and the trend looks set to continue in 2020. 2020-01-03-Zim.jpg A man holds a portrait of Robert Mugabe during his official funeral ceremony. Photo: Getty Images. Africa’s dinosaur leaders are members of an increasingly small and unstable club. Popular protests last year forced Algeria’s president, Abdelaziz Bouteflika, out of office after almost 20 years in power, as well as Sudan’s president, Omar al-Bashir, who ruled for 30 years. In 2017, Robert Mugabe was deposed in a military coup (although this was denied) after 40 years. And in 2011, mass protests led to the downfall of Tunisia’s president, Zine el-Abidine Ben Ali, after he had been in power for 23 years.Somewhat smoother are the political transitions in Angola and the Democratic Republic of the Congo (DRC). José Eduardo dos Santos, after almost 38 years in power, stepped down from office in 2017 as his term ended. So did his younger neighbour, Joseph Kabila, in January 2019, after 18 years in the presidency.What the six former leaders had in common was that they wanted to remain heads of state and considered succession planning or stepping down only as a last resort. This year will be crucial for the six countries in political transition particularly as the reform-window period is short.From A to Z Algeria: Tens of thousands of protesters have rallied in the capital Algiers and other cities against the December 2019 elections, rejecting what they see as sham transitional politics. A soft landing for Algeria in 2020 is unlikely, and what happens in the year has significant regional implications.Angola: A transition is under way, led by President João Lourenço. This shift is smoother than many others, but 2020 will be the watershed year. The country has been in economic recession for four years but is predicted to see gross domestic product growth in 2020. Investment and job creation will determine the pace of change. The honeymoon period has ended and there are signs of increasing frustration among the urban youth and the middle class.DRC: Despite his constitutionally mandated term expiring in December 2016, Joseph Kabila continued his presidency by continuously postponing elections until 30 December 2018. This election saw a three-way contest between the Union for Democracy and Social Progress (UDSP), the Engagement for Citizenship and Development party and the People’s Party for Reconstruction and Democracy (PPRD). Fèlix Tshisekedi of the UDSP was declared the winner by the Independent National Electoral Commission on January 10 last year with 38.6% votes. He was followed by Martin Fayulu of the Engagement for Citizenship and Development party, with 34.8%. He denounced the election results. In third place was Emmanuel Ramazani Shadary, of the PPRD, a key ally of Kabila.Although this was the first peaceful transition of power in DRC, there were widespread electoral inconsistencies and some observers believed that Fayulu was the legitimate winner. In 2020 it will become clearer whether a genuine transition from Kabila’s influence is taking place.Sudan: More promising than the DRC or Algeria, a 39-month transitional administration led by a technocratic prime minister, Abdalla Hamdok, has been established and enjoys domestic and international goodwill. This honeymoon is likely to be short, and the transitional administration needs to show results. The United States can help by removing Sudan from its terror list, thereby lifting the de facto ban on Sudan’s access to the dollar-based international financial system.Tunisia: A low-profile, conservative law professor beat a charismatic media magnate released from prison in the presidential election runoff in October 2019. Kais Saied won 70% of the vote and his victory and the putting together of a new governing coalition is another step forward in an open-ended democratic transition that started in 2011 after Ben Ali fell.Zimbabwe: This is a deeply troubled transition with an acute foreign exchange liquidity crisis, a deteriorating economy, hyperinflation and underperforming government. The state’s clinics and hospitals are closed or turn away patients as medical supplies run out and the doctors’ strike over decimated wages continues. There are power outages and almost half of the people face hunger and starvation as a result of drought and the economic crisis.Zimbabwe’s 2020 looks bleak, a far cry from the euphoria of two years ago when a “military assisted transition” removed Mugabe and replaced him with Emmerson Mnangagwa.More changes comingSo what do these political developments in 2019 tell us more broadly?Long-standing leaders have been persistent in Africa, despite the end of single-party rule in favour of a multiparty system. About a fifth of all African heads of state since independence can be classed as long-standing leaders — in power for more than a decade — and only five countries have never experienced one. But the trend is in decline.It remains most resilient in central Africa and in the Great Lakes regions. Cracks are appearing in their citadels in Malabo and Kampala, but in 2019 Equatorial Guinea’s President Teodoro Obiang Mbasogo celebrated 40 years in power and Uganda’s Yoweri Museveni 33 years.Will there be any more departures from the dinosaurs club in 2020?One of the shortest serving members of this club, President Pierre Nkurunziza (14 years in power) has said he will not stand for the 2020 elections in Burundi, although this is uncertain given that a 2018 constitutional referendum could allow him to stay in power until 2034. Togo’s Faure Gnassingbé (14 years in power) will stand for re-election to the presidency again after Parliament in 2019 approved a constitutional change permitting him to potentially stay in office until 2030.Amending constitutions to change term limits so that incumbent leaders can run for office is a favoured tactic. Rwanda’s Paul Kagame (19 years in office) and the Republic of Congo’s Denis Sassou Nguesso (25 years in power) have done this. But Eritrea’s Isaias Afwerki has never held an election during his 16 years in power.Attempts at dynasties have been less successful, such as with Grace Mugabe in Zimbabwe or Gamal Mubarak in Egypt, but Obiang is grooming his playboy son Teodorin to succeed him and Gabon’s Ali Bongo and Togo’s Gnassingbé both succeeded their fathers.The year is a reminder that more of these long-standing leaders will, in 2020 and beyond, step down or die. Most long-standing leaders in Africa are over the age of 70, with Paul Biya, aged 86, having served 37 years as Cameroon’s president.Some former leaders capitulated under internal pressure: in Algeria, Sudan, Tunisia and Zimbabwe. Only in Angola and the DRC was a transition process organized as part of an elite bargain.What the political transitions have in common is that honeymoons are short and that, whether they are led by interim administrations or elected leaders, they need to deliver political and socioeconomic improvements to succeed, but have inherited shambolic economies. Their success depends on accountable political leadership and domestic and international support.This article was originally published by the Mail & Guardian. Full Article
pp 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
pp Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer [Research] By feedproxy.google.com Published On :: 2020-02-01T00:05:29-08:00 Triple-negative breast cancer (TNBC) is characterized by poor response to therapy and low overall patient survival. Recently, Estrogen Receptor beta (ERβ) has been found to be expressed in a fraction of TNBCs where, because of its oncosuppressive actions on the genome, it represents a potential therapeutic target, provided a better understanding of its actions in these tumors becomes available. To this end, the cell lines Hs 578T, MDA-MB-468 and HCC1806, representing the claudin-low, basal-like 1 and 2 TNBC molecular subtypes respectively, were engineered to express ERβ under the control of a Tetracycline-inducible promoter and used to investigate the effects of this transcription factor on gene activity. The antiproliferative effects of ERβ in these cells were confirmed by multiple functional approaches, including transcriptome profiling and global mapping of receptor binding sites in the genome, that revealed direct negative regulation by ERβ of genes, encoding for key components of cellular pathways associated to TNBC aggressiveness representing novel therapeutic targets such as angiogenesis, invasion, metastasis and cholesterol biosynthesis. Supporting these results, interaction proteomics by immunoprecipitation coupled to nano LC-MS/MS mass spectrometry revealed ERβ association with several potential nuclear protein partners, including key components of regulatory complexes known to control chromatin remodeling, transcriptional and post-transcriptional gene regulation and RNA splicing. Among these, ERβ association with the Polycomb Repressor Complexes 1 and 2 (PRC1/2), known for their central role in gene regulation in cancer cells, was confirmed in all three TNBC subtypes investigated, suggesting its occurrence independently from the cellular context. These results demonstrate a significant impact of ERβ in TNBC genome activity mediated by its cooperation with regulatory multiprotein chromatin remodeling complexes, providing novel ground to devise new strategies for the treatment of these diseases based on ligands affecting the activity of this nuclear receptor or some of its protein partners. Full Article
pp Phosphoproteomic Approaches to Discover Novel Substrates of Mycobacterial Ser/Thr Protein Kinases [Reviews] By feedproxy.google.com Published On :: 2020-02-01T00:05:29-08:00 Mycobacterial Ser/Thr protein kinases (STPKs) play a critical role in signal transduction pathways that ultimately determine mycobacterial growth and metabolic adaptation. Identification of key physiological substrates of these protein kinases is, therefore, crucial to better understand how Ser/Thr phosphorylation contributes to mycobacterial environmental adaptation, including response to stress, cell division, and host-pathogen interactions. Various substrate detection methods have been employed with limited success, with direct targets of STPKs remaining elusive. Recently developed mass spectrometry (MS)-based phosphoproteomic approaches have expanded the list of potential STPK substrate identifications, yet further investigation is required to define the most functionally significant phosphosites and their physiological importance. Prior to the application of MS workflows, for instance, GarA was the only known and validated physiological substrate for protein kinase G (PknG) from pathogenic mycobacteria. A subsequent list of at least 28 candidate PknG substrates has since been reported with the use of MS-based analyses. Herein, we integrate and critically review MS-generated datasets available on novel STPK substrates and report new functional and subcellular localization enrichment analyses on novel candidate protein kinase A (PknA), protein kinase B (PknB) and PknG substrates to deduce the possible physiological roles of these kinases. In addition, we assess substrate specificity patterns across different mycobacterial STPKs by analyzing reported sets of phosphopeptides, in order to determine whether novel motifs or consensus regions exist for mycobacterial Ser/Thr phosphorylation sites. This review focuses on MS-based techniques employed for STPK substrate identification in mycobacteria, while highlighting the advantages and challenges of the various applications. Full Article
pp N-glycosylation Site Analysis Reveals Sex-related Differences in Protein N-glycosylation in the Rice Brown Planthopper (Nilaparvata lugens) [Research] By feedproxy.google.com Published On :: 2020-03-01T00:05:26-08:00 Glycosylation is a common modification of proteins and critical for a wide range of biological processes. Differences in protein glycosylation between sexes have already been observed in humans, nematodes and trematodes, and have recently also been reported in the rice pest insect Nilaparvata lugens. Although protein N-glycosylation in insects is nowadays of high interest because of its potential for exploitation in pest control strategies, the functionality of differential N-glycosylation between sexes is yet unknown. In this study, therefore, the occurrence and role of sex-related protein N-glycosylation in insects were examined. A comprehensive investigation of the N-glycosylation sites from the adult stages of N. lugens was conducted, allowing a qualitative and quantitative comparison between sexes at the glycopeptide level. N-glycopeptide enrichment via lectin capturing using the high mannose/paucimannose-binding lectin Concanavalin A, or the Rhizoctonia solani agglutinin which interacts with complex N-glycans, resulted in the identification of over 1300 N-glycosylation sites derived from over 600 glycoproteins. Comparison of these N-glycopeptides revealed striking differences in protein N-glycosylation between sexes. Male- and female-specific N-glycosylation sites were identified, and some of these sex-specific N-glycosylation sites were shown to be derived from proteins with a putative role in insect reproduction. In addition, differential glycan composition between males and females was observed for proteins shared across sexes. Both lectin blotting experiments as well as transcript expression analyses with complete insects and insect tissues confirmed the observed differences in N-glycosylation of proteins between sexes. In conclusion, this study provides further evidence for protein N-glycosylation to be sex-related in insects. Furthermore, original data on N-glycosylation sites of N. lugens adults are presented, providing novel insights into planthopper's biology and information for future biological pest control strategies. Full Article
pp Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome [Technological Innovation and Resources] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 Dynamic tyrosine phosphorylation is fundamental to a myriad of cellular processes. However, the inherently low abundance of tyrosine phosphorylation in the proteome and the inefficient enrichment of phosphotyrosine(pTyr)-containing peptides has led to poor pTyr peptide identification and quantitation, critically hindering researchers' ability to elucidate signaling pathways regulated by tyrosine phosphorylation in systems where cellular material is limited. The most popular approaches to wide-scale characterization of the tyrosine phosphoproteome use pTyr enrichment with pan-specific, anti-pTyr antibodies from a large amount of starting material. Methods that decrease the amount of starting material and increase the characterization depth of the tyrosine phosphoproteome while maintaining quantitative accuracy and precision would enable the discovery of tyrosine phosphorylation networks in rarer cell populations. To achieve these goals, the BOOST (Broad-spectrum Optimization Of Selective Triggering) method leveraging the multiplexing capability of tandem mass tags (TMT) and the use of pervanadate (PV) boost channels (cells treated with the broad-spectrum tyrosine phosphatase inhibitor PV) selectively increased the relative abundance of pTyr-containing peptides. After PV boost channels facilitated selective fragmentation of pTyr-containing peptides, TMT reporter ions delivered accurate quantitation of each peptide for the experimental samples while the quantitation from PV boost channels was ignored. This method yielded up to 6.3-fold boost in pTyr quantification depth of statistically significant data derived from contrived ratios, compared with TMT without PV boost channels or intensity-based label-free (LF) quantitation while maintaining quantitative accuracy and precision, allowing quantitation of over 2300 unique pTyr peptides from only 1 mg of T cell receptor-stimulated Jurkat T cells. The BOOST strategy can potentially be applied in analyses of other post-translational modifications where treatments that broadly elevate the levels of those modifications across the proteome are available. Full Article
pp Proximity Dependent Biotinylation: Key Enzymes and Adaptation to Proteomics Approaches [Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:26-07:00 The study of protein subcellular distribution, their assembly into complexes and the set of proteins with which they interact with is essential to our understanding of fundamental biological processes. Complementary to traditional assays, proximity-dependent biotinylation (PDB) approaches coupled with mass spectrometry (such as BioID or APEX) have emerged as powerful techniques to study proximal protein interactions and the subcellular proteome in the context of living cells and organisms. Since their introduction in 2012, PDB approaches have been used in an increasing number of studies and the enzymes themselves have been subjected to intensive optimization. How these enzymes have been optimized and considerations for their use in proteomics experiments are important questions. Here, we review the structural diversity and mechanisms of the two main classes of PDB enzymes: the biotin protein ligases (BioID) and the peroxidases (APEX). We describe the engineering of these enzymes for PDB and review emerging applications, including the development of PDB for coincidence detection (split-PDB). Lastly, we briefly review enzyme selection and experimental design guidelines and reflect on the labeling chemistries and their implication for data interpretation. Full Article
pp The mitochondrial protein PGAM5 suppresses energy consumption in brown adipocytes by repressing expression of uncoupling protein 1 [Metabolism] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression. Full Article
pp Sydney start-up Suppertime acquired by food delivery giant By www.smh.com.au Published On :: Mon, 12 Oct 2015 06:29:04 GMT Australian premium restaurant delivery service Suppertime has been snapped by a major international company, as the local food delivery market continues to heat up. Full Article
pp How Australian public service's digital reforms will happen, according to the Digital Transformation Office By www.smh.com.au Published On :: Thu, 15 Oct 2015 08:31:11 GMT The millions of customers, the short deadline: how the public service's digital revolution will start. Full Article
pp Centrelink blocks 60,000 calls a day, blames smartphone apps By www.smh.com.au Published On :: Fri, 23 Oct 2015 07:05:35 GMT Centrelink blocked 22m phone calls last year, with smartphone apps blamed for inflating the figures. Full Article
pp From AFL star to Big Apple start-up, Swift's Joel MacDonald is kicking goals By www.smh.com.au Published On :: Fri, 13 Nov 2015 05:53:09 GMT Two years ago Joel MacDonald was in Melbourne playing in the AFL; now he's kicking goals in New York. Full Article