rt Exploring Public International Law and the Rights of Individuals with Chinese Scholars - Part Two By feedproxy.google.com Published On :: Tue, 30 Oct 2018 08:46:37 +0000 15 November 2014 As part of a roundtable series, Chatham House and China University of Political Science and Law (CUPL) held a two-day roundtable meeting in Beijing on public international law and the rights of individuals. Download PDF Sonya Sceats Associate Fellow, International Law Programme @SonyaSceats 20140624ChinaHumanRights.jpg The Representative of China at the 19th Session of the Human Rights Council, Palais des Nations, Geneva. 27 February 2012. Photo: UN Photo Geneva/Violaine Martin. The specific objectives were to:create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China's role within it;support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.The roundtable forms part of a wider Chatham House project exploring China's impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.For CUPL, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.The meeting in Beijing was hosted by CUPL and involved 20 participants, 10 Chinese (from universities and other academic institutions in Beijing) and 10 non-Chinese (from Australia, the Netherlands, South Africa, Switzerland, the United Kingdom and the United States).To ensure continuity while also expanding the experts network being built, the second meeting included a mix of participants from the first meeting and some new participants.All discussions were held in English under the Chatham House Rule. Department/project International Law Programme, China and the Future of the International Legal Order Full Article
rt Exploring Public International Law and the Rights of Individuals with Chinese Scholars - Part Three By feedproxy.google.com Published On :: Tue, 30 Oct 2018 08:55:48 +0000 6 March 2016 As part of a roundtable series, Chatham House, China University of Political Science and Law (CUPL) and the Graduate Institute Geneva held a two-day roundtable meeting in Geneva on public international law and the rights of individuals. Download PDF Sonya Sceats Associate Fellow, International Law Programme @SonyaSceats 20140624ChinaHumanRights.jpg The Representative of China at the 19th Session of the Human Rights Council, Palais des Nations, Geneva. 27 February 2012. Photo: UN Photo Geneva/Violaine Martin. The specific objectives were to:create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China's role within it;support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.The roundtable forms part of a wider Chatham House project exploring China's impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.For CUPL, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.The meeting in Geneva was co-hosted by the Graduate Institute Geneva and involved 19 participants, 9 Chinese (from six research institutions in Beijing and Shanghai) and 11 non-Chinese (from eight research institutions in Australia, Germany, the Netherlands, Switzerland, the United Kingdom and the United States).To ensure continuity while also expanding the expert network being built, the third meeting included a mix of participants from the first two meetings and some new participantsAll discussions were held in English under the Chatham House Rule. Department/project International Law Programme, China and the Future of the International Legal Order Full Article
rt Exploring Public International Law Issues with Chinese Scholars – Part Four By feedproxy.google.com Published On :: Tue, 30 Oct 2018 09:01:59 +0000 3 June 2018 As part of a roundtable series, Chatham House and the China University of Political Science and Law (CUPL) held a two-day roundtable in Beijing on emerging issues of public international law. Download PDF Harriet Moynihan Senior Research Fellow, International Law Programme @HarrietMoyniha9 20140624ChinaHumanRights.jpg The Representative of China at the 19th Session of the Human Rights Council, Palais des Nations, Geneva. 27 February 2012. Photo: UN Photo Geneva/Violaine Martin. The specific objectives were to:create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China's role within it;support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.The roundtable forms part of a wider Chatham House project exploring China's impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.For CUPL, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.The meeting was co-hosted with CUPL and involved 28 participants, consisting of 19 Chinese participants (from six leading research institutions in Beijing and Shanghai) and nine nonChinese participants (from eight leading research institutions in Australia, the Netherlands, the UK, Switzerland, Canada and Singapore).To ensure continuity while also expanding the expert network being built, the fifth meeting included a mix of participants from the previous meetings and some new participants.All discussions were held in English under the Chatham House Rule. Department/project International Law Programme, China and the Future of the International Legal Order Full Article
rt Proportionality in the Conduct of Hostilities: The Incidental Harm Side of the Assessment By feedproxy.google.com Published On :: Thu, 06 Dec 2018 14:56:29 +0000 10 December 2018 Clarification of international humanitarian law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups is also crucial. Download PDF Emanuela-Chiara Gillard Associate Fellow, International Law Programme 2018-12-10-ilp-proportionality-paper.jpg Members of civil right defence conduct a search and rescue operation on destroyed buildings after an airstrike was carried out over the city of Jisr al-Shughur in Idlib province in Syria, on 6 May 2018. Photo: Hadi Harrat/Anadolu Agency/Getty Images. SummaryMilitary operations are taking place with increasing frequency in densely populated areas. Such operations result in loss of life and harm to civilians, as well as damage to civilian objects, (including infrastructure providing essential services). In order to protect civilians, it is imperative that armed forces and groups comply with the rules of international humanitarian law on the conduct of hostilities, including the rule of proportionality.The rule of proportionality prohibits attacks which may be expected to cause incidental loss of civilian life, injury to civilians, damage to civilian objects or a combination thereof, which would be excessive in relation to the concrete and direct military advantage anticipated. This research paper analyses the key steps that belligerents must take to give effect to the rule, with a particular focus on one side of proportionality assessments – the expected incidental harm.Those undertaking proportionality assessments before or during an attack must consider whether the expected harm will be caused by the attack, and whether that harm could be expected (that is, was it reasonably foreseeable).For the purpose of proportionality assessments, injury to civilians includes disease, and there is no reason in principle to exclude mental harm, even though it is currently challenging to identify and quantify it. Damage to civilian objects includes damage to elements of the natural environment.Once the incidental harm to be considered has been identified, a value or weight must be assigned to it. This is then balanced against the value or weight of the military advantage anticipated from the attack to determine whether the harm would be excessive.In the determination of whether the expected incidental harm would be excessive compared to the anticipated military advantage, ‘excessive’ is a wide but not indeterminate standard.Belligerents should develop methodologies so that those planning and deciding attacks are provided with all necessary information on expected incidental harm, and to assist them in assigning weight to the incidental harm to be considered.If it becomes apparent that the rule of proportionality will be contravened, the attack in question must be cancelled or suspended.Clarification of the law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups, inculcated by their leaders, is also crucial. Department/project International Law Programme, The Limits on War and Preserving the Peace Full Article
rt Strengthen the International Criminal Court By feedproxy.google.com Published On :: Fri, 31 May 2019 10:54:53 +0000 12 June 2019 Elizabeth Wilmshurst CMG Distinguished Fellow, International Law Programme The ICC has been criticized for slow proceedings, weak management and ineffective prosecutions. The good news is that pragmatic reform need not entail fundamental treaty amendment; a culture change and more realistic expectations would go a long way. 2016-02-22-Gbagbo2.jpg Laurent Gbagbo looks on next to his lawyer Emmanuel Altit before the start of his trial at the ICC on 28 January 2016. Photo by Getty Images. The 1998 treaty which established the International Criminal Court (ICC) was adopted at a time when the world (or most of it) was willing to reach multilateral agreements on a variety of topics and was encouraging the development of international criminal justice. The two tribunals, set up by the UN Security Council, for the former Yugoslavia and for Rwanda had been relatively successful. The time was ripe for states to agree together to set up a permanent international court with wider scope than the two tribunals.So the ICC was created, with jurisdiction over the international crimes of genocide, crimes against humanity and war crimes; its jurisdiction for the crime of aggression developed later. The court was given the power to prosecute nationals of states that were parties to the ICC Statute, and also to prosecute where the crime was committed in the territory of a state party, whatever the nationality of the alleged criminals. The court had further jurisdiction when the Security Council referred a situation to it.That was some 20 years ago. There is now a perception in many quarters that the ICC has not fulfilled the expectations of its founders. The court’s proceedings are cumbersome and lengthy. Many of the accused are still at large, including Omar al-Bashir, the former president of Sudan. Some €1.5 billion has been spent, and there have been only three convictions for the core international crimes.There have been criticisms of the judges, the former Prosecutor and other officials, as well as concern over particular decisions of the court. The allegation that the court is only interested in crimes in Africa[1] is perhaps heard less frequently now than it once was (most of the African governments concerned referred the situations in their countries to the ICC themselves), and there has not been the mass walk-out of African states that was once predicted. Our Shared Humanity: The Arc of Intervention From Bosnia to the Brahimi Report and from Rwanda to R2P, Annan played a significant role in many critical moments that shaped approaches to peacekeeping and to the protection of civilians. What was the impact? But in other quarters there is serious unease about the situation in the court. As the UK representative said at a meeting last year, ‘We cannot bury our heads in the sand and pretend everything is fine when it isn’t.’[2]The negative assessment of the ICC’s work may be countered by the fact that it is the failure of states to cooperate with the court that causes many of the problems. Further, the expectations of states and civil society about the possibilities of international criminal justice have been so high that no court would be able to meet them. It is not possible for one court actually to ‘end impunity’ for international crimes,[3] nor to prevent war-related violence and mass atrocities, nor to satisfy all victims.Moreover, the criticisms of the ICC come against the background of the global crisis for multilateralism more generally. The present US administration is notoriously hostile towards this international institution.[4]On the plus side, the establishment of the court has encouraged states to revise their own laws on international crimes and to institute their own prosecutions where it is possible to do so. It is also claimed that the very existence of the court can be a deterrent to potential perpetrators of international crimes. The court has begun to add to the body of international criminal law and has increased the possibility that mass atrocities will be investigated.But there is indeed some truth in the criticisms made of the internal workings of the court. One problem is that the particular combination of the civil and common law systems that has developed has produced cumbersome procedures regarding the representation of victims at most stages of the proceedings. It has also resulted in endless appeals from huge numbers of small decisions made by one chamber or another.Then there are the management failures which have led to officials of the court being awarded compensation by the administrative tribunal of the International Labour Organization (ILO) because of the way they were treated by the court, and finally the decision of a few of the judges to take proceedings themselves at the ILO to have their salaries increased. Some ICC decisions have been met with surprise. For example, a former vice-president of the Democratic Republic of the Congo, Jean-Pierre Bemba, who was in the custody of the ICC for 10 years, was convicted by a unanimous trial chamber of various crimes and then succeeded on his appeal. Following this and the acquittal of former Côte d’Ivoire president Laurent Gbagbo,[5] there are concerns about the ability of the prosecution to succeed in cases against high-level alleged perpetrators.Most recently, there has been criticism of the reasoning behind the appeal court decision regarding the immunity – or, rather, lack of immunity – of former president Bashir. And a decision of a chamber of the ICC not to authorize the opening of an investigation in Afghanistan has been seen as shielding the US from possible proceedings (though it has been welcomed by others as a pragmatic approach).The message that certain problems with the ICC need fixing is coming not just from the writings of academics and the legal blogs,[6] but from governments too, including those, like the UK, which are among the foremost supporters of the court.The former presidents of the ICC’s Assembly of States Parties (which comprises the representatives of all states parties) say that they ‘are disappointed by the quality of some of [the court’s] judicial proceedings, frustrated by some of the results, and exasperated by the management deficiencies that prevent the Court from living up to its full potential’.[7] Changes to remove the worst excesses of the procedures that have evolved could be effected without amendments to the treaty incorporating the ICC Statute. It may be that a change in culture is also needed. More modesty by the court, along with more realism from governments and civil society, is needed.And, attractive as it might seem to push at the boundaries of the law, the court should be realistic in what it can achieve. It is next to impossible to prosecute a case effectively where there is no cooperation from the state on whose territory the crimes were committed.What is needed is a court that can undertake efficient and effective criminal proceedings, delivering fair and impartial justice in the small number of cases which it is reasonable to expect it to address, in the light of the evidential challenges, limited resources and limited state cooperation.Governments should decide together at the Assembly of States Parties to set in hand a review of the ICC’s operations. It has been suggested that a group of experts might be mandated to assess the management of the court;[8] on the basis of their report, governments could agree on the necessary improvements.Not everything, however, can come within the remit of such a group. Governments should adopt new rules and practices to address matters such as the election process for judges and their training; governments might consider reaching their own understandings on how some provisions of the ICC Statute should be interpreted in practice. Governments should reach out to the many civil society organizations which have supported the court over the years, to ensure that they are involved in the process.Measures of this kind cannot detract from the fact that the ICC is fundamentally sound and that its role is as necessary as when it was first established. As Richard Goldstone, former chief prosecutor of the United Nations International Criminal Tribunals for the former Yugoslavia and Rwanda, has said, ‘If there were no ICC in existence today, many people in many countries would be agitating for and demanding one. That we have one is a singular achievement. It behoves us to make it the best possible and to assist it, as States, civil society, and individuals, in the best and most productive way possible.’[9]What needs to happenCumbersome procedures, ineffective prosecutions against high-level alleged perpetrators, and weak internal management are among current criticisms of the ICC.Improvements to the court’s effectiveness and credibility may be possible without amending the treaty incorporating the ICC Statute.The Assembly of States Parties should review the ICC’s operations, whether or not with a group of experts, and governments should agree on improvements.New rules and practices should address matters such as the election process for judges and their training.Better management of expectations of the ICC among governments, civil society and the court itself is needed.Governments might consider reaching their own understandings on how some provisions of the ICC Statute should be interpreted in practice.Civil society organizations should be involved in any procedures for reform.Notes[1] See, for example, du Plessis, M., Maluwa, T. and O’Reilly, A. (2013), Africa and the International Criminal Court, London: Royal Institute of International Affairs, July 2013, https://www.chathamhouse.org/publications/papers/view/193415.[2] GOV.UK (2018), ‘UK statement to ICC Assembly of States Parties 17th session’, 5 December 2018, https://www.gov.uk/government/speeches/uk-statement-to-icc-assembly-of-states-parties-17th-session.[3] As the preamble to the ICC Statute desires. See ICC (2011), Rome Statute of the International Criminal Court, p. 1, https://www.icc-cpi.int/resource-library/Documents/RS-Eng.pdf.[4] See the speech of John Bolton, US National Security Advisor. Just Security (2018), ‘Bolton’s Remarks on the International Criminal Court’, 10 September 2018, https://www.justsecurity.org/60674/national-security-adviser-john-bolton-remarks-international-criminal-court/.[5] Gbagbo was accused of various crimes which took place after Côte d’Ivoire’s election in 2010, in which Gbagbo lost power to Alassane Ouattara. The case was terminated by the court following a year’s hearings in which the prosecution put forward its evidence.[6] See, for example, Guilfoyle, D. (2019), ‘Reforming the International Criminal Court: Is it Time for the Assembly of State Parties to be the adults in the room?’, EJIL:Talk! blog post, 8 May 2019, https://www.ejiltalk.org/reforming-the-international-criminal-court-is-it-time-for-the-assembly-of-state-parties-to-be-the-adults-in-the-room/.[7] Al Hussein, Z. R., Stagno Ugarte, B., Wenaweser, C. and Intelman, T. (2019), ‘The International Criminal Court Needs Fixing’, Atlantic Council, 24 April 2019, https://www.atlanticcouncil.org/blogs/new-atlanticist/the-international-criminal-court-needs-fixing.[8] Ibid.[9] Goldstone, R. (2019), ‘Acquittals by the International Criminal Court’, EJIL:Talk! blog post, 18 January 2019, https://www.ejiltalk.org/acquittals-by-the-international-criminal-court/. Richard Goldstone is also a former justice of the Constitutional Court of South Africa.This essay was produced for the 2019 edition of Chatham House Expert Perspectives – our annual survey of risks and opportunities in global affairs – in which our researchers identify areas where the current sets of rules, institutions and mechanisms for peaceful international cooperation are falling short, and present ideas for reform and modernization. Full Article
rt In Judging Prorogation, UK Supreme Court Marks Evolution, Not Revolution, in Law By feedproxy.google.com Published On :: Thu, 03 Oct 2019 07:49:48 +0000 3 October 2019 Ruma Mandal Director, International Law Programme @RumaCHLaw Despite the political significance, last week’s judgment does not signal a newly activist court. 2019-10-03-UKSC.jpg The Supreme Court building in Westminster. Photo: Getty Images. The UK Supreme Court’s ruling last Wednesday has, at least temporarily, scuppered the prime minister’s plans to limit parliamentary debate before the looming Brexit deadline. Some of the prime minister’s allies have attacked the ruling as a ‘constitutional coup’. But a close reading reveals that the court has stayed within its remit to interpret, rather than make, the law.In a carefully reasoned judgment, the court emphasized that the case was not about Brexit. But the judges certainly did not shy away from the extraordinary nature of the matters before it, noting that such factual situations have ‘never arisen before and are unlikely ever to arise again… But our law is used to rising to such challenges and supplies us with the legal tools to enable us to reason to a solution.’The key question before the court was whether the prime minister’s decision to seek prorogation was ‘justiciable’ – i.e. amenable to being reviewed by a court. The English and Scottish courts earlier on in these proceedings had come, dramatically, to opposing views on this.The Supreme Court was not dissuaded by the inherently political considerations involved in the prime minister’s decision, stating that while ‘courts cannot decide political questions, the fact that a legal dispute concerns the conduct of politicians, or arises from a matter of political controversy, has never been sufficient reason for the courts to refuse to consider it’.The court went on to emphasize that the Crown’s remaining prerogative powers (exercised on the advice of the government or directly by ministers) have long been subject to judicial scrutiny; such oversight is essential to guarding the separation of powers underpinning the UK’s constitution.So far, so conventional. The full bench of the Supreme Court was required to grapple, though, with a prerogative power that had never been tested before in the courts. And so they delved back to the 1611 Case of Proclamations: ‘the King hath no prerogative, but that which the law of the land allow him’. In the court’s view, the legal issue to be resolved was the scope of the power to prorogue (the existence of this particular prerogative not being in dispute).With no case law available to provide direct guidance on this question, the court, instead, relied on two fundamental principles of the UK’s constitution – parliamentary sovereignty and parliamentary accountability. What would be the logical consequence of an unlimited power to prorogue? The ability to shut parliament permanently.The conclusion: this particular prerogative power had limits. The court held that:‘A decision to prorogue Parliament (or to advise the monarch to prorogue Parliament) will be unlawful if the prorogation has the effect of frustrating or preventing, without reasonable justification, the ability of Parliament to carry out its constitutional functions as a legislature and as the body responsible for the supervision of the executive. In such a situation, the court will intervene if the effect is sufficiently serious to justify such an exceptional course.’Having come to this conclusion, the court was left to examine what justification had in fact been given, noting that the prime minister’s motives were irrelevant. It noted that no clear reason had been given – the relevant documents were all concerned with preparing for the Queen’s speech.Noting evidence on normal practice for such preparations, including from a former prime minister, the court found it ‘impossible… to conclude…that there was any reason – let alone a good reason – to advise Her Majesty to prorogue Parliament for five weeks’.The court’s decision was neither inevitable nor a radical departure from legal tradition. It represents the gradual evolution of the long-established legal principle that the crown’s powers are set by the law and supervised by the courts.Courts have traditionally been reticent to rule on prerogative powers which are ‘high politics’ by nature – classic examples include declaring war and negotiating treaties. In recent years, though, the judiciary has shown a growing confidence to grapple with the contours of those prerogative powers that remain. Deference is still shown when looking at how those powers have been used as opposed to the limits of the prerogative in question.The Supreme Court ruling won’t reassure those who worry about the emergence of an activist court willing to wade (improperly) into the political arena. Nor will it necessarily bring comfort to those anxious about an unwritten constitution in an era where political conventions are fast unravelling.But divisive court rulings are nothing new, nor are ministerial outbursts about inconvenient judgments. In the current environment, politicians should take particular care not to send mixed messages which undermine the independence of the UK’s judiciary. Public trust in British institutions is dangerously low and the UK can ill-afford further damage to its reputation as a country steeped in democracy and the rule of law. Full Article
rt 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
rt 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
rt MtrP, a putative methyltransferase in Corynebacteria, is required for optimal membrane transport of trehalose mycolates [Lipids] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae. Full Article
rt Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes [Cell Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance. Full Article
rt Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis By feedproxy.google.com Published On :: 2020-04-01 Beatriz RochaApr 1, 2020; 19:574-588Research Full Article
rt Quantitative proteomics of human heart samples collected in vivo reveal the remodeled protein landscape of dilated left atrium without atrial fibrillation By feedproxy.google.com Published On :: 2020-04-14 Nora LinscheidApr 14, 2020; 0:RA119.001878v1-mcp.RA119.001878Research Full Article
rt Virtual Issue: Technological Innovations By feedproxy.google.com Published On :: 2020-04-01 Anne-Claude GingrasApr 1, 2020; 19:572-573Editorial Full Article
rt A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients By feedproxy.google.com Published On :: 2020-04-01 Dorte B. Bekker-JensenApr 1, 2020; 19:716-729Technological Innovation and Resources Full Article
rt Following the money in a massive “sextortion” spam scheme By feedproxy.google.com Published On :: Wed, 22 Apr 2020 12:30:08 +0000 Cryptocurrency profits from sextortion spam funneled into wallets tied to other cybercrime and dark web market activity. Full Article SophosLabs Uncut
rt Protecting the Cloud: Securing Windows Virtual Desktop By feedproxy.google.com Published On :: Fri, 24 Apr 2020 13:17:04 +0000 How to deploy and secure your virtual desktops with Sophos Intercept X and Sophos XG Firewall Full Article Cloud Cloud Security Intercept X Microsoft Azure XG Firewall XG Firewall v18
rt 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
rt 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
rt Smart Peace By feedproxy.google.com Published On :: Thu, 12 Sep 2019 08:59:39 +0000 With the number of violent conflicts increasing, there is a worldwide need to respond more effectively. Dialogue and mediation are proven to be effective in preventing and resolving conflicts, which are often complex, political and frequently-changing. But there is more to be done to understand how these approaches can adapt – responding quickly to changing politics and overcoming obstacles that block progress.Smart Peace is a global initiative led by Conciliation Resources, which combines the varied expertise of different consortium partners to address the challenges of building peace – focusing on the Central African Republic, Nigeria and Myanmar.This work combines peacebuilding techniques, conflict analysis, rigorous evaluation and behavioural insights. The resulting lessons will help communities, international organisations and governments to implement peace strategies with greater confidence.This project is funded with UK aid from the UK government.Smart Peace PartnersBehavioural Insights TeamConciliation ResourcesChatham HouseInternational Crisis GroupThe Asia FoundationThe Center for Security Studies at ETH ZurichThe Centre for Humanitarian Dialogue Department contact Nilza Amaral Project Manager, International Security Programme Email Latest (1) Research Event The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace 12 May 2020 Full Article
rt 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
rt 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
rt 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
rt Synergy in North Africa: Furthering Cooperation By feedproxy.google.com Published On :: Mon, 20 Jan 2020 15:57:54 +0000 21 January 2020 Discussions of North African integration have evoked ideas of a shared identity and a common destiny in the region. However, recent attempts to build regional blocs in North Africa have been unsuccessful. This paper examines the benefits of a ‘synergistic’ approach to North African cooperation. Read online Download PDF in English Download PDF in Arabic Dr Mohammed Masbah Associate Fellow, Middle East and North Africa Programme @MasbahMohammed LinkedIn Google Scholar Mohamed El Dahshan Associate Fellow, Middle East and North Africa Programme @eldahshan LinkedIn Google Scholar 2020-01-21-Market.jpg A Tunisian vendor poses as he sells white truffles at a market in the town of Ben Guerdane, 40km west of the Libyan border, in February 2016. Photo: Getty Images. SummaryNorth African integration is not a new idea. However, countries in the region have so far struggled to form a cohesive bloc with deep political, economic and social ties. Political instability has effectively deprioritized North African integration. A focus on thematic (political, economic and security) ‘synergies’ may provide a better framework for cooperation than seeking opportunities for all-encompassing ‘deep’ and ‘comprehensive’ integration.Governments of North Africa dedicate considerable resources to domestic security. Much of their efforts are conducted at the national-level and directed towards threats from terrorists, insurgents and militias. Improved security cooperation would achieve better outcomes and economies of scale, including efforts to tackle human trafficking.A new generation of jihadis has emerged in North Africa since 2011. Nearly 27 per cent of the 30,000 fighters who travelled to Syria are from the Maghreb. While government counterterrorism operations have been effective, countries have failed to address the root causes of radicalization.Border economies have suffered as a consequence of a security focus on terrorism and smuggling, which has rendered many previously accepted cross-border trade activities illegal. States have struggled to provide alternative livelihoods for those who have lost this source of income. Border forces tend to lack the right combination of capacity, training and equipment to secure borders and often resort to heavy-handed tactics.New thinking is required to develop a more human-centric and proactive approach to migration issues in the region, which continues to witness huge flows of migrants. The migration policy of Morocco, introduced through legislation in 2014, could be a model for North Africa.The countries of North Africa have varying economic profiles, ranging from economically diverse Morocco to oil-and-gas-dependant Libya. However, they all face similar challenges including unemployment (particularly among the young), poor public-service delivery, low FDI levels, an oversized public sector, ineffective tax collection, and high informality.Fostering entrepreneurship and the development of small and medium-sized enterprises (SMEs) are priorities for North African countries, particularly regarding job creation. Regulatory cooperation – such as harmonizing SME definitions, legislation and support institutions – across North Africa is an obvious area where further integration would encourage the development of start-ups and small businesses.With the advent of the fourth industrial revolution, North African governments must address their technological gaps and work to improve public–private cooperation. In some sectors, such as the fintech industry, North African countries can build upon nascent synergies that have developed organically, such as those of start-up incubators and angel investors that work across the region.Renewables, particularly solar energy production, are a promising development for North Africa. While regional initiatives, such as Desertec, have stalled due to political differences between countries, the sector has witnessed exponential growth in Tunisia, Egypt and Morocco, where the involvement of the private sector has proved successful. Department/project Middle East and North Africa Programme, North Africa Dialogues Full Article
rt 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
rt Webinar: Can the Justice and Development Party Still Absorb Popular Anger in Morocco? By feedproxy.google.com Published On :: Tue, 31 Mar 2020 13:50:01 +0000 Webinar Research Event 8 April 2020 - 1:00pm to 2:00pm Event participants Mohammed Masbah, Director, Moroccan Institute for Policy Analysis; Associate Fellow, MENA Programme, Chatham HouseModerator: Lina Khatib, Director, MENA Programme, Chatham House Ever since independence, the Moroccan monarchy has used political parties to legitimize the country’s authoritarian political process and structure, and to absorb social and political anger. The palace puts successive governments and other elected institutions, such as local and regional councils, at the frontline of public blame, and replaces them once they fail this function.In a recent article, MENA Programme Associate Fellow, Mohammed Masbah, examines how the Moroccan monarchy has used this strategy with the ruling Justice and Development Party (PJD) so that the palace remains the centre of political power, while the PJD – and other political parties before it– takes responsibility for coping with the mounting socio-economic crisis.In this webinar, part of the Chatham House project on The Future of the State in the Middle East and North Africa, the article’s author will discuss the risks this approach presents for the long-term stability of Morocco and what reforms are needed to increase citizens’ dwindling confidence in the political process.You can express your interest in attending by following this link. You will receive a Zoom confirmation email should your registration be successful. Department/project Middle East and North Africa Programme, The Future of the State in the Middle East Full Article
rt Virtual Roundtable: Russia in MENA By feedproxy.google.com Published On :: Wed, 01 Apr 2020 08:30:02 +0000 Invitation Only Research Event 3 April 2020 - 2:30pm to 3:30pm Event participants Nikolay Kozhanov, Research Associate Professor, Gulf Studies Center, Qatar University, Consulting Fellow, Russia and Eurasia Programme, Chatham HouseTim Eaton, Senior Research Fellow, Middle East and North Africa Programme, Chatham HouseChair: Sanam Vakil, Senior Research Fellow, Project Director, Future Dynamics of the Gulf, Middle East and North Africa Programme, Chatham House Russia’s Middle East policy is driven by a complex mixture of traditional factors (such as the ongoing confrontation with the West) and new trends. The Kremlin is keen to maintain its position as an influential external broker. However, it is not confident Russia would be able to respond effectively if forced into a reactive mode by other regional players. The Kremlin therefore seeks to retain initiative and shape the agenda according to its needs and resources. This makes prediction of Moscow’s next moves in the region a challenging, but not impossible, task.Nikolay Kozhanov will offer remarks on the changes that have taken place in Russia’s strategy since the publication of his research paper Russian Policy Across the Middle East: Motivations and Methods (2018), while Tim Eaton will explore Russia's increasing engagement in the Libyan conflict, and its now central role in Libya's diplomacy. Event attributes Chatham House Rule Department/project Russia and Eurasia Programme, Russian Foreign Policy Anna Morgan Administrator, Ukraine Forum +44 (0)20 7389 3274 Email Full Article
rt Webinar: Idlib at Risk – Doctors and First Responders in Northwest Syria By feedproxy.google.com Published On :: Thu, 16 Apr 2020 08:55:01 +0000 Members Event Webinar 23 April 2020 - 5:00pm to 6:00pm Online Event participants Dr Munzer al-Khalil, Head, Idlib Health DirectorateRaed Al Saleh, Director, Syria Civil Defence (The White Helmets)Alaa Rajaa Mughrabieh, Child Protection Officer, Hurras NetworkChair: Dr Lina Khatib, Director, Middle East and North Africa Programme, Chatham House In Syria, uncertainty about the safety of the ceasefire agreed between Russia and Turkey last month is inhibiting 1 million people who have been displaced since December 2019 from returning home.The looming COVID-19 global health crisis threatens to further devastate those most vulnerable as the conditions in northwest Syria’s refugee camps make it hard to practice common social distancing guidelines. Added to this, the medical infrastructure in the region has been decimated after years of bombings which has disabled over 70 health facilities since April 2019.This webinar highlights the potentially catastrophic risks of a coronavirus outbreak in Idlib and displacement camps in northwest Syria by speaking with medical and civil society actors working in the region. How are doctors and local humanitarian organizations scaling up their medical and prevention response to the COVID-19 outbreak?What key supplies such as ventilators, testing kits and critical sanitary equipment are still lacking? And how can the international community step in to help mitigate the potentially devastating consequences of an outbreak in these refugee camps?This event is run in collaboration with The Syria Campaign, a human rights organization working with Syrian civil society to raise the voices of those struggling for democracy, and support frontline activists and humanitarians. Full Article
rt 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
rt 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
rt 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
rt PARP-1-targeted Auger emitters display high-LET cytotoxic properties in vitro but show limited therapeutic utility in solid tumor models of human neuroblastoma By jnm.snmjournals.org Published On :: 2019-11-01T13:36:37-07:00 The currently available therapeutic radiopharmaceutical for high-risk neuroblastoma, 131I-MIBG, is ineffective at targeting micrometastases due to the low linear energy transfer (LET) properties of high-energy beta particles. In contrast, Auger radiation has high-LET properties with nanometer ranges in tissue, efficiently causing DNA damage when emitted in close proximity to DNA. The aim of this study was to evaluate the cytotoxicity of targeted Auger therapy in pre-clinical models of high-risk neuroblastoma. Methods: Using a radiolabeled poly(ADP-ribose) polymerase (PARP) inhibitor, 125I-KX1, we delivered an Auger emitter iodine-125 to PARP-1: a chromatin-binding enzyme overexpressed in neuroblastoma. In vitro cytotoxicity of 125I-KX1 was assessed in nineteen neuroblastoma cell lines, followed by in-depth pharmacological analysis in a sensitive and resistant pair of cell lines. Immunofluorescence microscopy was used to characterize 125I-KX1-induced DNA damage. Finally, in vitro/in vivo microdosimetry was modeled from experimentally derived pharmacological variables. Results: 125I-KX1 was highly cytotoxic in vitro across a panel of neuroblastoma cell lines, directly causing double strand DNA breaks. Based on subcellular dosimetry, 125I-KX1 was approximately twice as effective compared to 131I-KX1, whereas cytoplasmic 125I-MIBG demonstrated low biological effectiveness. Despite the ability to deliver focused radiation dose to the cell nuclei, 125I-KX1 remained less effective than its alpha-emitting analog 211At-MM4, and required significantly higher activity for equivalent in vivo efficacy based on tumor microdosimetry. Conclusion: Chromatin-targeted Auger therapy is lethal to high-risk neuroblastoma cells with potential use in micrometastatic disease. This study provides the first evidence for cellular lethality from a PARP-1 targeted Auger emitter, calling for further investigation into targeted Auger therapy. Full Article
rt 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
rt 11C-Methionine PET Identifies Astroglia Involvement in Heart-Brain Inflammation Networking after Acute Myocardial Infarction By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 Acute myocardial infarction (MI) triggers a local and systemic inflammatory response. We recently showed microglia involvement using TSPO imaging. Here, we evaluate whether 11C-methionine provides further insights into heart-brain inflammation networking. Methods: Male Bl6N mice underwent permanent coronary artery ligation followed by 11C-methionine PET at 3 and 7 days (n = 3). In subgroups, leukocyte homing was blocked by integrin antibodies (n = 5). The cellular substrate for PET signal was identified using brain section immunostaining. Results: 11C-methionine uptake peaked in the MI region at d3 (5.9±0.9vs 2.4±0.5 %ID/cc), decreasing to control level by d7 (4.3±0.6 %ID/cc). Brain uptake was proportional to cardiac uptake (r=0.47,p<0.05), peaking also at d3 (2.9±0.4vs 2.4±0.3 %ID/cc) and returning to baseline at d7 (2.3±0.4 %ID/cc). Integrin blockade reduced uptake at every time point. Immunostaining at d3 revealed co-localization of the L-type amino acid transporter with GFAP-positive astrocytes but not CD68-positive microglia. Conclusion: PET imaging with 11C-methionine specifically identifies an astrocyte component, enabling further dissection of the heart-brain axis in post MI inflammation. Full Article
rt 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
rt Light-induced radiosynthesis of 89ZrDFO-azepin-onartuzumab for imaging the hepatocyte growth factor receptor By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Methods that provide rapid access to radiolabeled antibodies are vital in the development of diagnostic and radiotherapeutic agents for positron emission tomography (PET) or radioimmunotherapy. The human hepatocyte growth factor receptor (c-MET) signaling pathway is dysregulated in a number of malignancies including gastric cancer, and is an important biomarker in drug discovery. Here, we used a photoradiochemical approach to produce 89Zr-radiolabeled onartuzumab (a monovalent, anti-human c-MET antibody), starting directly from the fully formulated drug (MetMAb). Methods: Simultaneous 89Zr-radiolabeling and protein conjugation was performed in one-pot reactions containing 89Zr-oxalate, the photoactive chelate DFO-aryl azide (DFO-ArN3) and MetMAb to give 89ZrDFO-azepin-onartuzumab. As a control, 89ZrDFO-Bn-NCS-onartuzumab was prepared via a conventional two-step process using pre-purified onartuzumab and DFO-Bn-NCS. Radiotracers were purified by using size-exclusion methods and evaluated by radiochromatography. Radiochemical stability was studied in human serum and immunoreactivity was determined by cellular binding assays using MKN-45 gastric carcinoma cells. PET imaging at multiple time points (0–72 h) was performed in female athymic nude mice bearing subcutaneous MKN-45 xenografts. Biodistribution experiments were performed after the final image. Tumor specificity of 89ZrDFO-azepin-onartuzumab was assessed by competitive inhibition (blocking) studies. Results: Initial photoradiosynthesis experiments produced 89ZrDFO-azepin-onartuzumab in <15 min. with an isolated decay-corrected radiochemical yield (RCY) of 24.8%, a radiochemical purity (RCP) ~90% and a molar activity (Am) of ~1.5 MBq nmol-1. Reaction optimization improved the radiochemical conversion (RCC) of 89ZrDFO-azepin-onartuzumab to 56.9±4.1% (n = 3), with isolated RCYs of 41.2±10.6% (n = 3), and RCPs >90%. Conventional methods produced 89ZrDFO-Bn-NCS-onartuzumab with isolated RCY >97%, RCP >97% and Am ~14.0 MBq nmol-1. Both radiotracers were immunoreactive and stable in human serum. PET imaging and biodistribution studies showed high tumor uptake for both radiotracers. By 72 h, tumor and liver uptake reached 15.37±5.21 %ID g-1, 6.56±4.03 %ID g-1, respectively for 89ZrDFO-azepin-onartuzumab (n = 4), and 21.38±11.57 %ID g-1 and 18.84±6.03 %ID g-1 for 89ZrDFO-Bn-NCS-onartuzumab (n = 4). Blocking experiments gave a statistically significant reduction in tumor uptake (6.34±0.47 %ID g-1) of 89ZrDFO-azepin-onartuzumab (n = 4). Conclusion: Experiments demonstrate that photoradiosynthesis is a viable alternative approach for producing 89Zr-radiolabeled antibodies direct in protein formulation buffer which reduces protein aggregation and liver uptake. Full Article
rt Demarcation of Sepsis-Induced Peripheral and Central Acidosis with pH-Low Insertion Cyclic (pHLIC) Peptide By jnm.snmjournals.org Published On :: 2020-01-31T13:36:41-08:00 Acidosis is a key driver for many diseases, including cancer, sepsis, and stroke. The spatiotemporal dynamics of dysregulated pH across disease remains elusive and current diagnostic strategies do not provide localization of pH alterations. We sought to explore if PET imaging using hydrophobic cyclic peptides that partition into the cellular membrane at low extracellular pH (denoted as "pHLIC") can permit accurate in vivo visualization of acidosis. Methods: Acid-sensitive cyclic peptide c[E4W5C] pHLIC was conjugated to bifunctional maleimide-NO2A and radiolabeled with copper-64 (t1/2 = 12.7 h). C57BL/6J mice were administered LPS (15 mg/kg) or saline (vehicle) and serially imaged with [64Cu]Cu-c[E4W5C] over 24 h. Ex vivo autoradiography was performed on resected brain slices and subsequently stained with cresyl violet to enable high-resolution spatial analysis of tracer accumulation. A non- pH-sensitive cell-penetrating control peptide (c[R4W5C]) was used to confirm specificity of [64Cu]Cu-c[E4W5C]. CD11b (macrophage/microglia) and TMEM119 (microglia) immunostaining was performed to correlate extent of neuroinflammation with [64Cu]Cu-c[E4W5C] PET signal. Results: [64Cu]Cu-c[E4W5C] radiochemical yield and purity was >95% and >99% respectively, with molar activity >0.925 MBq/nmol. Significantly increased [64Cu]Cu-c[E4W5C] uptake was observed in LPS-treated mice (vs. vehicle) within peripheral tissues including blood, lungs, liver, and small intestines (P < 0.001-0.05). Additionally, there was significantly increased [64Cu]Cu-c[E4W5C] uptake in the brains of LPS-treated animals. Autoradiography confirmed increased uptake in the cerebellum, cortex, hippocampus, striatum, and hypothalamus of LPS-treated mice (vs. vehicle). Immunohistochemical (IHC) analysis revealed microglial/macrophage infiltrate, suggesting activation in brain regions containing increased tracer uptake. [64Cu]Cu-c[R4W5C] demonstrated significantly reduced uptake in the brain and periphery of LPS mice compared to the acid-mediated [64Cu]Cu-c[E4W5C] tracer. Conclusion: Here, we demonstrate that a pH-sensitive PET tracer specifically detects acidosis in regions associated with sepsis-driven pro-inflammatory responses. This study suggests that [64Cu]Cu-pHLIC is a valuable tool to noninvasively assess acidosis associated with both central and peripheral innate immune activation. Full Article
rt PET/CT imaging with a 18F-labeled galactodendritic unit in a galectin-1 overexpressing orthotopic bladder cancer model By jnm.snmjournals.org Published On :: 2020-01-31T13:36:41-08:00 Galectins are carbohydrate-binding proteins overexpressed in bladder cancer (BCa) cells. Dendritic galactose moieties have a high affinity for galectin-expressing tumor cells. We radiolabeled a dendritic galactose carbohydrate with fluorine-18 – 18F-labeled galactodendritic unit 4 – and examined its potential in imaging urothelial malignancies. Methods: The 18F-labeled 1st generation galactodendritic unit 4 was obtained from its tosylate precursor. We conducted in vivo studies in galectin-expressing UMUC3 orthotopic BCa model to determine the ability of 18F-labeled galactodendritic unit 4 to image BCa. Results: Intravesical administration of 18F-labeled galactodendritic unit 4 allowed specific accumulation of the carbohydrate radiotracer in galectin-1 overexpressing UMUC3 orthotopic tumors when imaged with PET. The 18F-labeled galactodendritic unit 4 was not found to accumulate in non-tumor murine bladders. Conclusion: The 18F-labeled galactodendritic unit 4 and similar analogs may be clinically relevant and exploitable for PET imaging of galectin-1 overexpressing bladder tumors. Full Article
rt FDG-PET/CT identifies predictors of survival in patients with locally advanced cervical carcinoma and para-aortic lymph node involvement to increase treatment By jnm.snmjournals.org Published On :: 2020-02-07T14:31:42-08:00 Introduction: To use positron emission tomography coupled with computed tomography (18FDG-PET/CT) to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy (EFR) between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynaecologic oncology reviewed all 18FDG-PET/CT scans. Metabolic parameters including maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were determined for the primary tumour, pelvic lymph nodes and PALN. Associations between these parameters and overall survival (OS) were assessed with Cox's proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% CI (40.8-68.0)). When adjusted for age, stage and histology, pelvic lymph node TLG, PALN TLG and PALN SUVmax were significantly associated with OS (p<0.005). Conclusion: FDG-PET/CT was able to identify predictors of survival in the homogeneous subgroup of patients with LACC and PALN involvement, thus allowing therapeutic intensification to be proposed. Full Article
rt Prognostic Value of 18F-FDG PET/CT in a Large Cohort of 495 Patients with Advanced Metastatic Neuroendocrine Neoplasms (NEN) Treated with Peptide Receptor Radionuclide Therapy (PRRT) By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 The objective of this retrospective study was to determine the role of 18F-FDG PET/CT in a large cohort of 495 patients with metastatic neuroendocrine neoplasms (NENs) who were treated with peptide receptor radionuclide therapy (PRRT) with a long-term follow-up. Methods: The 495 patients were treated with 177Lu- and/or 90Y- DOTATOC/DOTATATE PRRT between 2/2002 and 7/2018. All subjects received both 68Ga-DOTATOC/TATE/NOC and 18F-FDG PET/CT prior to treatment and were followed 3-189 months. Kaplan-Meier analysis, log-rank test (Mantel-Cox), and Cox regression analysis were performed for overall survival (OS) and progression-free survival (PFS). Results: 199 patients (40.2%) presented with pancreatic NEN, 49 with CUP (cancer of unknown primary), 139 with midgut NEN, whereas the primary tumor was present in the rectum in 20, in the lung in 38, in the stomach in 8 and other locations in 42 patients. FDG-PET/CT was positive in 382 (77.2%) patients and 113 (22.8%) were FDG-negative before PRRT, while 100% were 68Ga-DOTATOC/TATE/NOC positive. For all patients, the median PFS and OS, defined from start of PRRT, were 19.6 mo and 58.7 mo, respectively. Positive FDG predicted shorter PFS (18.5 mo vs 24.1 mo; P = 0.0015) and OS (53.2 mo vs 83.1 mo; P < 0.001) than negative FDG. Amongst the pancreatic NEN, the median OS was 52.8 mo in FDG positive and 114.3 mo in FDG negative subjects (P = 0.0006). For all patients with positive 18F-FDG uptake, and a ratio of the highest SUVmax on 68Ga-SSTR PET to the most 18F-FDG-avid tumor lesions >2, the median OS was 53.0 mo, compared to 43.4 mo in those patients with a ratio <2 (P = 0.030). For patients with no 18F-FDG uptake (complete "mismatch" imaging pattern), the median OS was 108.3 mo vs 76.9 mo for SUVmax >15.0 and ≤15.0 on 68Ga-SSTR PET/CT, respectively. Conclusion: The presence of positive lesions on 18F-FDG PET is an independent prognostic factor in patients with NEN treated with PRRT. Metabolic imaging with 18F-FDG PET/CT compliments the molecular imaging aspect of 68Ga-SSTR PET/CT for the prognosis of survival after PRRT. High SSTR expression combined with negative 18F-FDG PET/CT imaging is associated with the most favorable long-term prognosis. Full Article
rt Defining hyper-progressive disease using tumor growth rate: what are limitations and shortcuts? By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 Full Article
rt 18F-DCFPyL PET/CT in Patients with Subclinical Recurrence of Prostate Cancer: Effect of Lesion Size, Smooth Filter and Partial Volume Correction on Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria By jnm.snmjournals.org Published On :: 2020-03-20T13:59:23-07:00 Purpose: To determine the effect of smooth filter and partial volume correction (PVC) method on measured prostate-specific membrane antigen (PSMA) activity in small metastatic lesions and to determine the impact of these changes on the molecular imaging (mi) PSMA scoring. Materials & Methods: Men with biochemical recurrence of prostate cancer with negative CT and bone scintigraphy were referred for 18F-DCFPyL PET/CT. Examinations were performed on one of 2 PET/CT scanners (GE Discovery 610 or Siemens mCT40). All suspected tumor sites were manually contoured on co-registered CT and PET images, and each was assigned a miPSMA score as per the PROMISE criteria. The PVC factors were calculated for every lesion using the anatomical CT and then applied to the unsmoothed PET images. The miPSMA scores, with and without the corrections, were compared, and a simplified "rule of thumb" (RoT) correction factor (CF) was derived for lesions at various sizes (<4mm, 4-7mm, 7-9mm, 9-12mm). This was then applied to the original dataset and miPSMA scores obtained using the RoT CF were compared to those found using the actual corrections. Results: There were 75 men (median age, 69 years; median serum PSA of 3.69 ug/L) with 232 metastatic nodes < 12 mm in diameter (mean lesion volume of 313.5 ± 309.6 mm3). Mean SUVmax before and after correction was 11.0 ± 9.3 and 28.5 ± 22.8, respectively (p<0.00001). The mean CF for lesions <4mm (n = 22), 4-7mm (n = 140), 7-9mm (n = 50), 9-12 mm (n = 20) was 4 (range: 2.5-6.4), 2.8 (range: 1.6-4.9), 2.3 (range: 1.6-3.3) and 1.8 (range 1.4-2.4), respectively. Overall miPSMA scores were concordant between the corrected dataset and RoT in 205/232 lesions (88.4%). Conclusion: There is a significant effect of smooth filter and partial volume correction on measured PSMA activity in small nodal metastases, impacting the miPSMA score. Full Article
rt Benefit of improved performance with state-of-the art digital PET/CT for lesion detection in oncology By jnm.snmjournals.org Published On :: 2020-03-20T13:59:23-07:00 Latest digital whole-body PET scanners provide a combination of higher sensitivity and improved spatial and timing resolution. We performed a lesion detectability study on two generations of Siemens Biograph PET/CT scanners, the mCT and Vision, to study the impact of improved physical performance on clinical performance. Our hypothesis is that the improved performance of the Vision will result in improved lesion detectability, allowing shorter imaging times or equivalently, lower injected dose. Methods: Data were acquired with the Society of Nuclear Medicine and Molecular Imaging Clinical Trials Network torso phantom combined with a 20-cm diameter cylindrical phantom. Spherical lesions were emulated by acquiring spheres-in-air data, and combining it with the phantom data to generate combined datasets with embedded lesions of known contrast. Two sphere sizes and uptakes were used: 9.89 mm diameter spheres with 6:1 (lung) and 3:1 (cylinder) and 4.95 mm diameter spheres with 9.6:1 (lung) and 4.5:1 (cylinder) local activity concentration uptakes. Standard image reconstruction was performed: ordinary Poisson ordered subsets expectation maximization algorithm with point spread function and time-of-flight modeling and post-reconstruction smoothing with a 5 mm Gaussian filter. The Vision images were also generated without any post-reconstruction smoothing. Generalized scan statistics methodology was used to estimate the area under the localization receiver operating characteristic curve (ALROC). Results: Higher sensitivity and improved TOF performance of Vision leads to reduced contrast in the background noise nodule distribution. Measured lesion contrast is also higher on the Vision due to its improved spatial resolution. Hence, the ALROC values are noticeably higher for the Vision relative to the mCT. Conclusion: Improved overall performance of the Vision provides a factor of 4-6 reduction in imaging time (or injected dose) over the mCT when using the ALROC metric for lesions >9.89 mm in diameter. Smaller lesions are barely detected in the mCT, leading to even higher ALROC gains with the Vision. Improved spatial resolution of the Vision also leads to a higher measured contrast that is closer to the real uptake, implying improved quantification. Post-reconstruction smoothing, however, reduces this improvement in measured contrast, thereby reducing the ALROC values for small, high uptake lesions. Full Article
rt A Prospective, Comparative Study of Planar and Single-photon Emission Computed Tomography Ventilation/Perfusion Imaging for Chronic Thromboembolic Pulmonary Hypertension By jnm.snmjournals.org Published On :: 2020-03-20T13:59:23-07:00 Objectives: The study compared the diagnostic performance of Planar Ventilation/perfusion (V/Q) and V/Q Single-photon computed tomography (SPECT), and determined whether combining perfusion scanning with low-dose computed tomography (Q-LDCT) may be equally effective in a prospective study of patients with chronic thromboembolic pulmonary hypertension (CTEPH) patients. Background: V/Q scanning is recommended for excluding CTEPH during the diagnosis of pulmonary hypertension (PH). However, Planar V/Q and V/Q SPECT techniques have yet to be compared in patients with CTEPH. Methods: Patients with suspected PH were eligible for the study. PH attributable to left heart disease or lung disease was excluded, and patients whose PH was confirmed by right heart catheterization and who completed Planar V/Q, V/Q-SPECT, Q-LDCT, and pulmonary angiography were included. V/Q images were interpreted and patients were diagnosed as instructed by the 2009 EANM guidelines, and pulmonary angiography analyses were used as a reference standard. Results: A total of 208 patients completed the study, including 69 with CTEPH confirmed by pulmonary angiography. Planar V/Q, V/Q-SPECT, and Q-LDCT were all highly effective for diagnosing CTEPH, with no significant differences in sensitivity or specificity observed among the three techniques (Planar V/Q [sensitivity/specificity]: 94.20%/92.81%; V/Q-SPECT: 97.10%/91.37%, Q-LCDT: 95.65%/90.65%). However, V/Q-SPECT was significantly more sensitive (V/Q-SPECT: 79.21%; Planar V/Q: 75.84%, P = 0.012; Q-LDCT: 74.91%, p<0.001), and Planar V/Q was significantly more specific (Planar V/Q: 54.14%; V/Q-SPECT 46.05%, p<0.001; Q-LDCT: 46.05%, P = 0.001) than the other two techniques for identifying perfusion defects in individual lung segments. Conclusion: Both Planar V/Q and V/Q-SPECT were highly effective for diagnosing CTEPH, and Q-LDCT may be a reliable alternative method for patients who are unsuitable for ventilation imaging. Full Article
rt Letter to the Editor: Who was the first doctor to report the Covid-19 outbreak in Wuhan, China? By jnm.snmjournals.org Published On :: 2020-04-17T08:32:41-07:00 Full Article
rt 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
rt The Impact of Radiobiologically-Informed Dose Prescription on the Clinical Benefit of Yttrium-90 SIRT in Colorectal Cancer Patients By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 The purpose of this study was to establish the dose-response relationship of selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC), when informed by radiobiological sensitivity parameters derived from mCRC cell lines exposed to yttrium-90 (90Y). Methods: 23 mCRC patients with liver metastases refractory to chemotherapy were included. 90Y bremsstrahlung SPECT images were transformed into dose maps assuming the local dose deposition method. Baseline and follow-up CT scans were segmented to derive liver and tumor volumes. Mean, median, and D70 (minimum dose to 70% of tumor volume) values determined from dose maps were correlated with change in tumor volume and vRECIST response using linear and logistic regression, respectively. Radiosensitivity parameters determined by clonogenic assays of mCRC cell lines HT-29 and DLD-1 after exposure to 90Y or external beam radiotherapy (EBRT; 6MV photons) were used in biological effective dose (BED) calculations. Results: Mean administered radioactivity was 1469±428 MBq (847-2185 MBq), achieving a mean radiation absorbed tumor dose of 35.5±9.4 Gy and mean normal liver dose of 26.4±6.8 Gy. A 1.0 Gy increase in mean, median, and D70 absorbed dose was associated with reduction in tumor volume of 1.8%, 1.8%, and 1.5%, respectively, and increased probability of vRECIST response (odds ratio: 1.09, 1.09, and 1.10 respectively). Threshold mean, median and D70 doses for response were 48.3, 48.8, and 41.8 Gy respectively. EBRT-equivalent BEDs for 90Y are up to 50% smaller than those calculated by applying protraction-corrected radiobiological parameters derived from EBRT alone. Conclusion: Dosimetric studies have assumed equivalence between 90Y SIRT and EBRT, leading to inflation of BED for SIRT and possible under-treatment. Radiobiological parameters for 90Y were applied to a BED model, providing a calculation method that has the potential to improve assessment of tumor control. Full Article
rt Reshaping the amyloid buildup curve in Alzheimer's disease? - Partial volume effect correction of longitudinal amyloid PET data By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 It was hypothesized that the brain β-amyloid buildup curve plateaus at an early symptomatic Alzheimer's disease (AD) stage. Atrophy-related partial volume effects (PVEs) degrade signal in hot-spot imaging techniques, such as amyloid positron emission tomography (PET). This longitudinal analysis of amyloid-sensitive PET data investigated the shape of the β-amyloid curve in AD applying PVE correction (PVEC). We analyzed baseline and 2-year follow-up data of 216 symptomatic individuals on the AD continuum (positive amyloid status) enrolled in Alzheimer's Disease Neuroimaging Initiative (17 AD dementia, 199 mild cognitive impairment), including 18F-florbetapir PET, magnetic resonance imaging and mini mental state examination (MMSE) scores. For PVEC, the modified Müller-Gärtner method was performed. Compared to non-PVE-corrected data, PVE-corrected data yielded significantly higher regional and composite standardized uptake value ratio (SUVR) changes over time (P=0.0002 for composite SUVRs). Longitudinal SUVR changes in relation to MMSE decreases showed a significantly higher slope of the regression line in the PVE-corrected as compared to the non-PVE-corrected PET data (F=7.1, P=0.008). These PVEC results indicate that the β-amyloid buildup curve does not plateau at an early symptomatic disease stage. A further evaluation of the impact of PVEC on the in-vivo characterization of time-dependent AD pathology, including the reliable assessment and comparison of other amyloid tracers, is warranted. Full Article
rt Unexplained Hyperthyroglobulinemia in Differentiated Thyroid Cancer Patients Indicates Radioiodine Adjuvant Therapy: A Prospective Multicenter Study By jnm.snmjournals.org Published On :: 2020-05-01T11:16:58-07:00 Background: The management for totally thyroidectomized differentiated thyroid cancer (TT-DTC) patients with unexplained hyperthyroglobulinemia remains indeterminate due to evidence scarcity. This multicenter study aimed at prospectively evaluating the response to radioiodine (131I) adjuvant therapy (RAT) and its potential role in risk stratification and causal clarification. Methods: TT-DTC patients with stimulated serum thyroglobulin (Tgoff) levels > 10 ng/mL but no structurally evident disease were consecutively enrolled in five tertiary care institutions. After the administration of 5.55 GBq of 131I, the risk of presence of persistent/recurrent/metastatic DTC (prmDTC) was compared to that before RAT. The causes of hyperthyroglobulinemia were explored and the response to RAT was assessed 6-12 months post RAT. The change in suppressed thyroglobulin (Tgon) level was reported. Results: A cohort of 254 subjects with a median Tgoff of 27.1 ng/mL was enrolled for the analyses. Immediately after RAT, low-, intermediate-, and high-risk were identified in 5.9%, 88.6%, and 5.5% patients, respectively, with no significant difference in risk stratification compared with that before RAT (P = 0.952). During the follow-up (median, 10.6 months), hyperthyroglobulinemia was ultimately attributed to thyroid remnant, biochemical disease, and structural/functional disease in 17.3%, 54.3%, and 28.3% of subjects, respectively. In addition, excellent, indeterminate, biochemical incomplete, and structural/functional incomplete responses were achieved in 18.1%, 27.2%, 36.2%, and 18.5% of patients, respectively. Notably, distribution for either cause of hyperthyroglobulinemia or response to RAT was comparable among the three postoperative risk groups. Tgon levels in patients who merely received RAT declined significantly over time. Conclusion: Our study demonstrated that over 90% of TT-DTC patients with unexplained hyperthyroglobulinemia are stratified as intermediate-high risk, and RAT using 5.55 GBq of 131I reveals biochemical/functional/structural disease and yields non-structural/functional incomplete response in more than 80% patients, suggesting TT-DTC patients with unexplained hyperthyroglobulinemia as explicit candidates for RAT. Full Article
rt Reported differences between Digital and Analog PET/CT studies By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 Full Article
rt Central and Eastern Europe and Sub-Saharan Africa: The Potential of Investment Partnerships for Mutual Benefit By feedproxy.google.com Published On :: Thu, 31 Oct 2019 08:54:39 +0000 31 October 2019 Trade between Central and Eastern Europe and sub-Saharan Africa has increased significantly in the last decade and a half. There is a strong case to be made for greater economic re-engagement, especially in terms of investment, that has the potential to support inclusive growth in both regions. Read online Download PDF Damir Kurtagic Former Academy Robert Bosch Fellow, Africa Programme @kurtagic_damir LinkedIn recycled-containerboard-warehouse_mondi_poland.jpg Recycled containerboard warehouse, Mondi Group, Poland. Photo: Mondi Group. SummaryThere are growing economic links between the economies of Central and Eastern Europe and sub-Saharan Africa in terms of both trade and investment. However, while trade has picked up significantly from pre-EU accession levels, investment has not increased to the same extent.Contrary to common assumption, investment flows are not solely from Central and Eastern Europe to sub-Saharan Africa. In reality, the largest investment flow between the two blocs occurs in the opposite direction – from South Africa into Central and Eastern Europe.Sub-Saharan Africa can benefit from a greater commercial relationship focused on attracting sustainable investment from Central and Eastern Europe. For this to happen, commercial strategies towards Central and Eastern European countries need to be put in place before strategy can be reinforced by greater diplomatic and informational support.For many sub-Saharan African governments, there is no overall targeted approach to attracting Central and Eastern European investors. A notable exception is South Africa, where departments have been established at provincial government level to specifically target investment from Central and Eastern Europe.Sub-Saharan African governments expect Central and Eastern European private-sector investment to result not only in job creation, but also to bring spillover benefits such as the transfer of skills and knowledge to domestic industries.Each sub-Saharan African country, in accordance with its individual circumstances, will need to adopt a discrete mix of administrative reform (particularly aimed at cutting red tape), as well as infrastructural and other policies that improve the business environment and generate investor confidence.Much of the private sector in Central and Eastern Europe is somewhat hesitant to invest in sub-Saharan Africa on a greater scale. Many companies are most comfortable operating within their domestic environment; when they invest abroad, it tends to be in the ‘neighbourhood’ with which they are already familiar. Perceptions of risk are often compounded by popular misperceptions and generalizations about sub-Saharan Africa.Central and Eastern European countries stand to gain from a deeper investment relationship. While greater engagement with sub-Saharan Africa has already been pursued by some countries, most of them focus on trade. Institutional support to companies from Central and Eastern Europe (both public and private) has evolved to a degree, but is still not comprehensive. Information for companies interested in investing is either lacking or not shared in an efficient way. And the greatest challenge is ensuring top-level political engagement.EU membership offers clear opportunities for Central and Eastern European countries to invest sustainably and responsibly in sub-Saharan Africa. Not only is financial support forthcoming, through innovative EU financial instruments, but the availability of information relevant to business and the EU’s extensive diplomatic presence in Africa should help to alleviate some of the concerns of Central and Eastern European investors. Department/project Africa Programme, Foreign Relations and Africa’s Agency in the International System, Inclusive Economic Growth, Governance and Technology Full Article