nfl Kruppel-like factor 3 (KLF3) suppresses NF-{kappa}B-driven inflammation in mice [Immunology] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 Bacterial products such as lipopolysaccharides (or endotoxin) cause systemic inflammation, resulting in a substantial global health burden. The onset, progression, and resolution of the inflammatory response to endotoxin are usually tightly controlled to avoid chronic inflammation. Members of the NF-κB family of transcription factors are key drivers of inflammation that activate sets of genes in response to inflammatory signals. Such responses are typically short-lived and can be suppressed by proteins that act post-translationally, such as the SOCS (suppressor of cytokine signaling) family. Less is known about direct transcriptional regulation of these responses, however. Here, using a combination of in vitro approaches and in vivo animal models, we show that endotoxin treatment induced expression of the well-characterized transcriptional repressor Krüppel-like factor 3 (KLF3), which, in turn, directly repressed the expression of the NF-κB family member RELA/p65. We also observed that KLF3-deficient mice were hypersensitive to endotoxin and exhibited elevated levels of circulating Ly6C+ monocytes and macrophage-derived inflammatory cytokines. These findings reveal that KLF3 is a fundamental suppressor that operates as a feedback inhibitor of RELA/p65 and may be important in facilitating the resolution of inflammation. Full Article
nfl NIH clinical trial tests remdesivir plus anti-inflammatory drug baricitinib for COVID-19 By www.eurekalert.org Published On :: Fri, 08 May 2020 00:00:00 EDT (NIH/National Institute of Allergy and Infectious Diseases) A randomized, controlled clinical trial evaluating the safety and efficacy of a treatment regimen of the investigational antiviral remdesivir plus the anti-inflammatory drug baricitinib for COVID-19 has begun. The trial is now enrolling hospitalized adults with COVID-19 in the United States. The trial is expected to open at approximately 100 US and international sites. Investigators currently anticipate enrolling more than 1,000 participants. The National Institute of Allergy and Infectious Diseases is sponsoring the trial. Full Article
nfl Study: Climate change has been influencing where tropical cyclones rage By www.eurekalert.org Published On :: Mon, 04 May 2020 00:00:00 EDT (NOAA Headquarters) While the global average number of tropical cyclones each year has not budged from 86 over the last four decades, climate change has been influencing the locations of where these deadly storms occur, according to new NOAA-led research published in Proceedings of the National Academy of Science. Full Article
nfl URI professor: Climate change increases risk of fisheries conflict By www.eurekalert.org Published On :: Mon, 04 May 2020 00:00:00 EDT (University of Rhode Island) A team of experts, led by a University of Rhode Island researcher, examined how climate change is affecting the ocean environment and found that the changing conditions will likely result in increased fisheries-related conflicts and create new challenges in the management of global fisheries. Full Article
nfl Family Conflict and Diabetes Management in Youth: Clinical Lessons From Child Development and Diabetes Research By spectrum.diabetesjournals.org Published On :: 2004-01-01 Barbara J. AndersonJan 1, 2004; 17:Articles Full Article
nfl Armed Conflict and Starvation: What Does the Law Say? By feedproxy.google.com Published On :: Wed, 18 Jul 2018 15:05:01 +0000 Research Event 12 October 2018 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Professor Dapo Akande, Co-Director, Oxford Institute for Ethics, Law and Armed Conflict Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham HouseAhila Sornarajah, Senior Lawyer, International and EU LawChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House Millions of civilians suffer hunger and starvation in times of armed conflict. This panel discusses the legal prohibitions on the use of starvation as a method of war, and the obligations on the warring parties to allow access for humanitarian relief. Department/project International Law Programme Chanu Peiris Programme Manager, International Law +44 (0)20 7314 3686 Email Full Article
nfl Protection of the Wounded and Medical Care-Givers in Armed Conflict: Is the Law Up to the Job? By feedproxy.google.com Published On :: Wed, 27 Feb 2019 10:21:55 +0000 Research Event 16 May 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Françoise Bouchet-Saulnier, Legal Director, Médecins Sans FrontièresEzequiel Heffes, Thematic Legal Adviser, Geneva CallRain Liivoja, Associate Professor, University of QueenslandMaciej Polkowski, Head, Health Care in Danger Initiative, International Committee of the Red CrossChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House This meeting, supported by the British Red Cross, is the first in a series of three to commemorate the 70th anniversary of the 1949 Geneva Conventions. The meeting will focus on the protection of the wounded and sick in armed conflict and will also include discussion of challenges to the protection of medical care and of health providers.Attacks on health care personnel and facilities have increased in recent years, as have the instances in which proceedings have been brought against those providing medical care to wounded fighters, including under counter-terrorism measures.The Geneva Conventions and their Protocols give protection to the wounded and sick and to healthcare providers, but is the law adequate? Is the law sufficiently widely known? How can the law be more fully implemented? What particular challenges arise in non-international armed conflicts?This event will be followed by a drinks reception. Department/project International Law Programme, The Limits on War and Preserving the Peace Full Article
nfl The Protection of Children in Armed Conflict By feedproxy.google.com Published On :: Tue, 25 Jun 2019 18:10:01 +0000 Research Event 25 September 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham HouseJoanne Neenan, Legal Adviser, UK Foreign and Commonwealth OfficeDarren Stewart, Head of Operational Law, UK Army HeadquartersChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House With more protracted and urbanized conflicts, the character of warfare is changing in a manner that is having a greater impact on children. Aside from physical harm, they face the trauma of family separation and displacement, are vulnerable to sexual abuse and recruitment as soldiers and suffer severe disruption to their education. This event will discuss how international humanitarian law applies to the protection of children. Are offences against children in armed conflict being prosecuted adequately? Are there better ways of ensuring compliance with the law?This meeting is the second in a series of three commemorating the 70th anniversary of the 1949 Geneva Conventions.This event, which is supported by the British Red Cross, will be followed by a drinks reception.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Department/project International Law Programme, The Limits on War and Preserving the Peace Chanu Peiris Programme Manager, International Law +44 (0)20 7314 3686 Email Full Article
nfl Protecting Children in Conflict: See Me Safe Symposium By feedproxy.google.com Published On :: Wed, 01 May 2019 14:55:01 +0000 Invitation Only Research Event 7 May 2019 - 10:00am to 5:00pm Chatham House, London Today there are 420 million children, or one-fifth of children worldwide, who live in conflict zones and are at risk of being killed or injured and denied access to education, healthcare and humanitarian assistance. From Myanmar and Syria, to South Sudan and Yemen, the impact of conflict on children and their families is devastating. With conflicts becoming more protracted and urbanized, and the undermining of international rules and norms, the risk to civilians is rapidly increasing. The impact of the crisis in civilian protection is not only devastating children’s lives and risking a lost generation, it threatens global stability and prosperity, contributing to the degradation of the international rules-based system and its institutions and undermining the ability to hold perpetrators accountable and prevent these atrocities from happening. This symposium will bring together practitioners, policymakers, business leaders, philanthropists and academics for a day of panel discussions on the protection of children in conflict. The aim of the event is to generate an informed debate and to deepen engagement with issues around protecting children in conflict as well as to inspire support to help rebuild children’s lives. This event will be followed by a reception from 17:00-18:30. Attendance is by invitation only. Celebrating its centenary in 2020, Chatham House is partnering with Save the Children on this core area of their work, in their anniversary year. Department/project International Security Programme Nilza Amaral Project Manager, International Security Programme Email Full Article
nfl Local Pathways Towards De-escalation of Libya's Conflict By feedproxy.google.com Published On :: Wed, 22 Jan 2020 10:20:01 +0000 Invitation Only Research Event 28 January 2020 - 3:00pm to 4:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Usama Otman Essed, Libya Center for Strategic & Future StudiesChair: Tim Eaton, Middle East and North Africa Programme, Chatham House A shaky truce remains broadly in place among rival Libyan forces fighting for control of Tripoli. However, a durable ceasefire to bring an end to the current bout of conflict, which was initiated by Khalifa Haftar’s Libyan Arab Armed Forces’ (LAAF) offensive on the capital in April 2019, has not been reached. In recent weeks attention has focused on talks hosted in Moscow and Berlin, with the former aimed at agreeing a ceasefire and the latter seeking to reach agreement among international actors to bring an end to external military support for Libyan warring actors, and to craft a way forward for future intra-Libyan talks. Yet, there has been little emphasis on Libyan actors – beyond Haftar and prime minister Fayez al-Serraj – in this process. This roundtable will bring together experts and policymakers to discuss means of de-escalating the conflict and seeking a lasting resolution through the development of interconnected intra-Libyan social and security negotiation tracks. Mr Usama Otman Essed of the Libya Center for Strategic and Future Studies (LCSFS) will present his research group’s ideas on these issues and discuss their ongoing efforts to promote dialogue among social and security actors.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme 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
nfl Conflict and the Water Crisis in Iraq By feedproxy.google.com Published On :: Mon, 24 Feb 2020 13:15:01 +0000 Invitation Only Research Event 9 March 2020 - 9:00am to 10:30am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Dr Azzam Alwash, Founder & CEO, Nature IraqPeter Schwartzstein, Independent Journalist; Non-Resident Fellow, Centre for Climate SecurityDiscussant: Dr Jehan Baban, Founder & President, The Iraqi Environment and Health Society-UKChair: Dr Glada Lahn, Senior Research Fellow, Energy, Environment and Resources Department, Chatham House Water is a critical issue for Iraq’s future stability and prosperity. Only a few decades ago, the country was one of the most fertile in the region, with two major rivers flowing through it. Today, national and transboundary pollution, mismanagement, and debilitating cycles of conflict have contributed to a situation where only half of current water needs are being met, and where an 80% reduction in the flow of water down the Tigris and Euphrates rivers has led to the loss of millions of acres of formerly productive land and the displacement of rural communities.Water scarcity can be a driver of violence and conflict. Tribal conflicts over water sources have erupted sporadically in the south and the contamination of municipal water which led to the hospitalization of some 118,000 citizens was a trigger for the large-scale protests in Basra in late 2018. Without concerted action by national and local governments, companies and international agencies, the situation will only worsen as higher temperatures and reduced rainfall drive rural-to-urban migration and increase the risk of drought, food insecurity and water-related diseases.At this roundtable, part of the Chatham House Iraq Initiative, experts will discuss the domestic, regional and international factors that continue to exacerbate the water crisis in Iraq, and propose solutions, including technical innovation, public sector capacity-building and greater international cooperation, that might contribute to effective state-building, build resilience to the effects of climate change and reduce the risk of further conflict. Event attributes Chatham House Rule Department/project Middle East and North Africa Programme, Iraq Initiative Georgia Cooke Project Manager, Middle East and North Africa Programme +44 (0)20 7957 5740 Email Full Article
nfl 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
nfl Inflammation-based index and 68Ga-DOTATOC PET-derived uptake and volumetric parameters predict outcome in neuroendocrine tumor patients treated with 90Y-DOTATOC By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 We performed post-hoc analyses on the utility of pre-therapeutic and early interim 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammation-based index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with 90Y-DOTATOC in the setting of a prospective phase II trial. Methods: Forty-three NET patients received up to four cycles of 1.85 GBq/m²/cycle 90Y-DOTATOC with a maximal kidney biologic effective dose of 37 Gy. All patients underwent a 68Ga-DOTATOC PET/computed tomography (CT) at baseline and seven weeks after the first PRRT cycle. 68Ga-DOTATOC-avid tumor lesions were semi-automatically delineated using a customized standardized uptake value (SUV) threshold-based approach. PRRT response was assessed on CT using RECIST 1.1. Results: Median progression-free survival (PFS) and overall survival (OS) were 13.9 and 22.3 months, respectively. An SUVmean higher than 13.7 (75th percentile (P75)) was associated with better survival (hazard ratio (HR) 0.45; P = 0.024), whereas a 68Ga-DOTATOC-avid tumor volume higher than 578 ml (P75) was associated with worse OS (HR 2.18; P = 0.037). Elevated baseline IBI was associated with worse OS (HR 3.90; P = 0.001). Multivariate analysis corroborated independent associations between OS and SUVmean (P = 0.016) and IBI (P = 0.015). No significant correlations with PFS were found. A composite score based on SUVmean and IBI allowed to further stratify patients in three categories with significantly different survival. On early interim PET, a decrease in SUVmean of more than 17% (P75) was associated with worse survival (HR 2.29; P = 0.024). Conclusion: Normal baseline IBI and high 68Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with 90Y-DOTATOC. This can be used for treatment personalization. Interim 68Ga-DOTATOC PET does not provide information for treatment personalization. Full Article
nfl Influencing the social impact of financial systems: alternative strategies By feedproxy.google.com Published On :: Wed, 04 Mar 2020 13:35:39 +0000 4 March 2020 , Volume 96, Number 2 Lee-Anne Sim Read Online The social impact of the global financial crisis brought global and domestic financial systems into public focus. While over the last ten years governments have introduced a range of regulatory reforms, there are still low levels of public trust in financial sectors, and academics continue to express their concerns about financial systems and their desire for more influence. This is particularly the case for those framing their evaluation of the quality of financial systems in terms of social values. This article offers those seeking more influence over the social values of financial systems, a fresh perspective on their available strategic options for influencing outcomes. It argues that they should consider strategies aimed at making allies of financial sectors and regulators in influencing change. The main advantage of these alliance strategies is that they address key constraints to influence, as identified in existing scholarship, which are difficult to relax because they are tied to features inherent in financial systems. By addressing these constraints, alliance strategies could increase the likelihood that financial system outcomes align more closely with their preferred social values. Full Article
nfl ICC’s Influence Can Be Strengthened by Ukraine’s Case By feedproxy.google.com Published On :: Wed, 22 Apr 2020 22:27:35 +0000 22 April 2020 Kateryna Busol Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @KaterynaBusol LinkedIn Second in a two-part series analysing why Ukraine’s attempts at international justice are worth taking - and outlining how the impact goes far beyond just the Russia-Ukraine conflict. Part two examines Ukraine’s appeal to the International Criminal Court (ICC) to seek individual criminal responsibility of the alleged perpetrators of the gravest crimes in occupied Crimea and eastern Ukraine. 2020-04-23-Ukraine-Anniversary-Conflict Marking the Day of The National Flag of Ukraine, a day before celebrations of the anniversary of state independence. Photo by ANATOLII STEPANOV/AFP via Getty Images. The recognition by Ukraine of the jurisdiction of the International Criminal Court (ICC) to consider grave crimes allegedly perpetrated in its territory has led to the ICC Prosecutor’s preliminary examination identifying a wave of alleged war crimes and crimes against humanity.There are claims of persecution, forced conscription, deportation, sham trials, enforced disappearances, and property seizure - in Crimea. As well as killings, torture, inhuman treatment, sexual violence, and indiscriminate shelling - in Donbas. The court now needs to decide whether to open a full investigation which could lead to charges against specific individuals, as in the trial currently taking place in the Netherlands over MH-17.However, the ICC does remain a court of last resort as Ukraine retains the principal power to prosecute grave violations perpetrated in its eastern regions and Crimea, with the court only stepping in if Ukraine (or another court with jurisdiction) is either unwilling or unable to do so.As the evidence mounts up, Ukrainian investigators, prosecutors and judges are becoming more open to cooperation with foreign experts, law firms, human rights NGOs and younger domestic professionals - a significant proportion of whom are women.Transformation shows determinationThis is an unusual shift, given the rigid hierarchical nature of post-Soviet institutions, with elderly males in most of the top positions. The transformation shows the determination to see perpetrators of crimes in Crimea and Donbas tried by the ICC, with joint professional development trainings and joint communications about the alleged crimes.Ukraine has also been strengthening its institutions. The Prosecutor’s Office of the Autonomous Republic of Crimea has been improving quality control of its war crime proceedings, and has taken a strong pro-ICC stance. The Office of the Prosecutor General established a special department to monitor the armed conflict proceedings, and two specialised war crime units have been formed in Donbas.Although too early to assess progress - given recent prosecution reform and that much-needed legislation on international crimes is still pending – these are promising signs of Ukraine’s intent to take a specialised approach to armed conflict violations. And Ukrainian civil society organisations are also playing a more important role, documenting alleged crimes and sending evidence to the ICC.Any intervention by the ICC in Ukraine also has a considerable impact on the wider dynamics of addressing international crimes, further extending the court’s reach beyond a focus on Africa which has attracted widespread criticism since it began in 2002.The ICC has already opened investigations in Georgia, Bangladesh/Myanmar, and Afghanistan, with preliminary examinations in Colombia, Venezuela, Iraq/UK, Palestine, and The Philippines. But the Ukrainian case would further develop the European subtleties of the court’s jurisprudence.Although the ICC is currently investigating the 2008 Russia-Georgia war, the active phase of that armed conflict lasted for just five days whereas Russia’s military involvement in Ukraine has been ongoing for the six years. The temporal difference in no way diminishes the suffering of victims and the necessity for the proper investigation, prosecution and compensation in the Georgian context.And yet, going by even the preliminary findings of the ICC prosecutor, the spectrum of war crimes and crimes against humanity allegedly perpetrated in Ukraine is much wider. Some incidents, such as the illegal construction of the Crimean Bridge, is an amalgam of the violations against property, cultural heritage and the environment. Cumulatively, the Ukrainian and Georgian cases would substantially contribute to the development of the court’s emerging European lenses.The Russia-Ukraine armed conflict is also the first instance of armed hostilities of such magnitude and duration in Europe since World War II and the Yugoslav Wars. The ICC’s readiness to take on such geopolitically challenging cases which leave itself open to attack will be tested.But by examining new contexts - including Ukraine - the ICC would develop a more layered reading of the nature and scope of the crimes it works on. For example, alleged indoctrination and use of children by armed groups in eastern Ukraine is likely to differ from the known practices of abducting and recruiting child soldiers in Africa.Investigating evidence of Russia’s persecution of pro-Ukrainian activists - forcing them out of Crimea - coupled with the creation of favourable conditions for Russian citizens to relocate to Crimea could lead to proving the existence of a policy of mass colonisation of the peninsula - adding new layers to the court’s jurisprudence on population displacement. And previously under-prosecuted crimes may come to the fore, such as attacks on cultural property or causing the destruction of the environment.Although the ICC proceedings on Ukraine – along with those being held by the International Court of Justice (ICJ) - are unlikely to bring immediate results, Ukraine has developed an international adjudication strategy based on the available viable options and what can be practically delivered.The simple act of a reputed international court outlining Russia’s alleged violations in Crimea and Donbas and naming those individually responsible would be an impactful achievement in itself, regardless of whether Russia pays any attention or compensation.And any international judgments or those of domestic courts such as the Dutch MH-17 proceedings and Russia’s response - predicted to be non-compliance - is an important argument for continuing sanctions against Russia over its conduct in Ukraine.The mutually reinforcing effect of both the Crimea and Donbas proceedings within Ukraine and at international courts should not be underestimated. These investigations into war crimes, terrorism and human rights issues are deeply relevant - not only for the conflict itself, but also for the development of international law.Part One of this series assesses Ukraine’s efforts to hold Russia accountable as a state at the International Court of Justice (ICJ). Full Article
nfl ICC’s Influence Can Be Strengthened by Ukraine’s Case By feedproxy.google.com Published On :: Wed, 22 Apr 2020 22:27:35 +0000 22 April 2020 Kateryna Busol Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @KaterynaBusol LinkedIn Second in a two-part series analysing why Ukraine’s attempts at international justice are worth taking - and outlining how the impact goes far beyond just the Russia-Ukraine conflict. Part two examines Ukraine’s appeal to the International Criminal Court (ICC) to seek individual criminal responsibility of the alleged perpetrators of the gravest crimes in occupied Crimea and eastern Ukraine. 2020-04-23-Ukraine-Anniversary-Conflict Marking the Day of The National Flag of Ukraine, a day before celebrations of the anniversary of state independence. Photo by ANATOLII STEPANOV/AFP via Getty Images. The recognition by Ukraine of the jurisdiction of the International Criminal Court (ICC) to consider grave crimes allegedly perpetrated in its territory has led to the ICC Prosecutor’s preliminary examination identifying a wave of alleged war crimes and crimes against humanity.There are claims of persecution, forced conscription, deportation, sham trials, enforced disappearances, and property seizure - in Crimea. As well as killings, torture, inhuman treatment, sexual violence, and indiscriminate shelling - in Donbas. The court now needs to decide whether to open a full investigation which could lead to charges against specific individuals, as in the trial currently taking place in the Netherlands over MH-17.However, the ICC does remain a court of last resort as Ukraine retains the principal power to prosecute grave violations perpetrated in its eastern regions and Crimea, with the court only stepping in if Ukraine (or another court with jurisdiction) is either unwilling or unable to do so.As the evidence mounts up, Ukrainian investigators, prosecutors and judges are becoming more open to cooperation with foreign experts, law firms, human rights NGOs and younger domestic professionals - a significant proportion of whom are women.Transformation shows determinationThis is an unusual shift, given the rigid hierarchical nature of post-Soviet institutions, with elderly males in most of the top positions. The transformation shows the determination to see perpetrators of crimes in Crimea and Donbas tried by the ICC, with joint professional development trainings and joint communications about the alleged crimes.Ukraine has also been strengthening its institutions. The Prosecutor’s Office of the Autonomous Republic of Crimea has been improving quality control of its war crime proceedings, and has taken a strong pro-ICC stance. The Office of the Prosecutor General established a special department to monitor the armed conflict proceedings, and two specialised war crime units have been formed in Donbas.Although too early to assess progress - given recent prosecution reform and that much-needed legislation on international crimes is still pending – these are promising signs of Ukraine’s intent to take a specialised approach to armed conflict violations. And Ukrainian civil society organisations are also playing a more important role, documenting alleged crimes and sending evidence to the ICC.Any intervention by the ICC in Ukraine also has a considerable impact on the wider dynamics of addressing international crimes, further extending the court’s reach beyond a focus on Africa which has attracted widespread criticism since it began in 2002.The ICC has already opened investigations in Georgia, Bangladesh/Myanmar, and Afghanistan, with preliminary examinations in Colombia, Venezuela, Iraq/UK, Palestine, and The Philippines. But the Ukrainian case would further develop the European subtleties of the court’s jurisprudence.Although the ICC is currently investigating the 2008 Russia-Georgia war, the active phase of that armed conflict lasted for just five days whereas Russia’s military involvement in Ukraine has been ongoing for the six years. The temporal difference in no way diminishes the suffering of victims and the necessity for the proper investigation, prosecution and compensation in the Georgian context.And yet, going by even the preliminary findings of the ICC prosecutor, the spectrum of war crimes and crimes against humanity allegedly perpetrated in Ukraine is much wider. Some incidents, such as the illegal construction of the Crimean Bridge, is an amalgam of the violations against property, cultural heritage and the environment. Cumulatively, the Ukrainian and Georgian cases would substantially contribute to the development of the court’s emerging European lenses.The Russia-Ukraine armed conflict is also the first instance of armed hostilities of such magnitude and duration in Europe since World War II and the Yugoslav Wars. The ICC’s readiness to take on such geopolitically challenging cases which leave itself open to attack will be tested.But by examining new contexts - including Ukraine - the ICC would develop a more layered reading of the nature and scope of the crimes it works on. For example, alleged indoctrination and use of children by armed groups in eastern Ukraine is likely to differ from the known practices of abducting and recruiting child soldiers in Africa.Investigating evidence of Russia’s persecution of pro-Ukrainian activists - forcing them out of Crimea - coupled with the creation of favourable conditions for Russian citizens to relocate to Crimea could lead to proving the existence of a policy of mass colonisation of the peninsula - adding new layers to the court’s jurisprudence on population displacement. And previously under-prosecuted crimes may come to the fore, such as attacks on cultural property or causing the destruction of the environment.Although the ICC proceedings on Ukraine – along with those being held by the International Court of Justice (ICJ) - are unlikely to bring immediate results, Ukraine has developed an international adjudication strategy based on the available viable options and what can be practically delivered.The simple act of a reputed international court outlining Russia’s alleged violations in Crimea and Donbas and naming those individually responsible would be an impactful achievement in itself, regardless of whether Russia pays any attention or compensation.And any international judgments or those of domestic courts such as the Dutch MH-17 proceedings and Russia’s response - predicted to be non-compliance - is an important argument for continuing sanctions against Russia over its conduct in Ukraine.The mutually reinforcing effect of both the Crimea and Donbas proceedings within Ukraine and at international courts should not be underestimated. These investigations into war crimes, terrorism and human rights issues are deeply relevant - not only for the conflict itself, but also for the development of international law.Part One of this series assesses Ukraine’s efforts to hold Russia accountable as a state at the International Court of Justice (ICJ). Full Article
nfl Role of pyruvate kinase M2 in oxidized LDL-induced macrophage foam cell formation and inflammation [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Pyruvate kinase M2 (PKM2) links metabolic and inflammatory dysfunction in atherosclerotic coronary artery disease; however, its role in oxidized LDL (Ox-LDL)-induced macrophage foam cell formation and inflammation is unknown and therefore was studied. In recombinant mouse granulocyte-macrophage colony-stimulating factor-differentiated murine bone marrow-derived macrophages, early (1–6 h) Ox-LDL treatment induced PKM2 tyrosine 105 phosphorylation and promotes its nuclear localization. PKM2 regulates aerobic glycolysis and inflammation because PKM2 shRNA or Shikonin abrogated Ox-LDL-induced hypoxia-inducible factor-1α target genes lactate dehydrogenase, glucose transporter member 1, interleukin 1β (IL-1β) mRNA expression, lactate, and secretory IL-1β production. PKM2 inhibition significantly increased Ox-LDL-induced ABCA1 and ABCG1 protein expression and NBD-cholesterol efflux to apoA1 and HDL. PKM2 shRNA significantly inhibited Ox-LDL-induced CD36, FASN protein expression, DiI-Ox-LDL binding and uptake, and cellular total cholesterol, free cholesterol, and cholesteryl ester content. Therefore, PKM2 regulates lipid uptake and efflux. DASA-58, a PKM2 activator, downregulated LXR-α, ABCA1, and ABCG1, and augmented FASN and CD36 protein expression. Peritoneal macrophages showed similar results. Ox-LDL induced PKM2- SREBP-1 interaction and FASN expression in a PKM2-dependent manner. Therefore, this study suggests a role for PKM2 in Ox-LDL-induced aerobic glycolysis, inflammation, and macrophage foam cell formation. Full Article
nfl Hepatic PLIN5 signals via SIRT1 to promote autophagy and prevent inflammation during fasting [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Lipid droplets (LDs) are energy-storage organelles that are coated with hundreds of proteins, including members of the perilipin (PLIN) family. PLIN5 is highly expressed in oxidative tissues, including the liver, and is thought to play a key role in uncoupling LD accumulation from lipotoxicity; however, the mechanisms behind this action are incompletely defined. We investigated the role of hepatic PLIN5 in inflammation and lipotoxicity in a murine model under both fasting and refeeding conditions and in hepatocyte cultures. PLIN5 ablation with antisense oligonucleotides triggered a pro-inflammatory response in livers from mice only under fasting conditions. Similarly, PLIN5 mitigated lipopolysaccharide- or palmitic acid-induced inflammatory responses in hepatocytes. During fasting, PLIN5 was also required for the induction of autophagy, which contributed to its anti-inflammatory effects. The ability of PLIN5 to promote autophagy and prevent inflammation were dependent upon signaling through sirtuin 1 (SIRT1), which is known to be activated in response to nuclear PLIN5 under fasting conditions. Taken together, these data show that PLIN5 signals via SIRT1 to promote autophagy and prevent FA-induced inflammation as a means to maintain hepatocyte homeostasis during periods of fasting and FA mobilization. Full Article
nfl Composition-function analysis of HDL subpopulations: influence of lipid composition on particle functionality [Research Articles] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 The composition-function relationship of HDL particles and its effects on the mechanisms driving coronary heart disease (CHD) is poorly understood. We tested the hypothesis that the functionality of HDL particles is significantly influenced by their lipid composition. Using a novel 3D-separation method, we isolated five different-sized HDL subpopulations from CHD patients who had low preβ-1 functionality (low-F) (ABCA1-dependent cholesterol-efflux normalized for preβ-1 concentration) and controls who had either low-F or high preβ-1 functionality (high-F). Molecular numbers of apoA-I, apoA-II, and eight major lipid classes were determined in each subpopulation by LC-MS. The average number of lipid molecules decreased from 422 in the large spherical α-1 particles to 57 in the small discoid preβ-1 particles. With decreasing particle size, the relative concentration of free cholesterol (FC) decreased in α-mobility but not in preβ-1 particles. Preβ-1 particles contained more lipids than predicted; 30% of which were neutral lipids (cholesteryl ester and triglyceride), indicating that these particles were mainly remodeled from larger particles not newly synthesized. There were significant correlations between HDL-particle functionality and the concentrations of several lipids. Unexpectedly, the phospholipid:FC ratio was significantly correlated with large-HDL-particle functionality but not with preβ-1 functionality. There was significant positive correlation between particle functionality and total lipids in high-F controls, indicating that the lipid-binding capacity of apoA-I plays a major role in the cholesterol efflux capacity of HDL particles. Functionality and lipid composition of HDL particles are significantly correlated and probably both are influenced by the lipid-binding capacity of apoA-I. Full Article
nfl Lipid rafts in glial cells: role in neuroinflammation and pain processing [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-01T00:05:27-07:00 Activation of microglia and astrocytes secondary to inflammatory processes contributes to the development and perpetuation of pain with a neuropathic phenotype. This pain state presents as a chronic debilitating condition and affects a large population of patients with conditions like rheumatoid arthritis and diabetes, or after surgery, trauma, or chemotherapy. Here, we review the regulation of lipid rafts in glial cells and the role they play as a key component of neuroinflammatory sensitization of central pain signaling pathways. In this context, we introduce the concept of an inflammaraft (i-raft), enlarged lipid rafts harboring activated receptors and adaptor molecules and serving as an organizing platform to initiate inflammatory signaling and the cellular response. Characteristics of the inflammaraft include increased relative abundance of lipid rafts in inflammatory cells, increased content of cholesterol per raft, and increased levels of inflammatory receptors, such as toll-like receptor (TLR)4, adaptor molecules, ion channels, and enzymes in lipid rafts. This inflammaraft motif serves an important role in the membrane assembly of protein complexes, for example, TLR4 dimerization. Operating within this framework, we demonstrate the involvement of inflammatory receptors, redox molecules, and ion channels in the inflammaraft formation and the regulation of cholesterol and sphingolipid metabolism in the inflammaraft maintenance and disruption. Strategies for targeting inflammarafts, without affecting the integrity of lipid rafts in noninflammatory cells, may lead to developing novel therapies for neuropathic pain states and other neuroinflammatory conditions. Full Article
nfl ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surface [Membrane Biology] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily O-glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte–EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation. Full Article
nfl Amylin/Calcitonin Receptor-Mediated Signaling in POMC Neurons Influences Energy Balance and Locomotor Activity in Chow-Fed Male Mice By diabetes.diabetesjournals.org Published On :: 2020-03-09T12:48:09-07:00 Amylin, a pancreatic hormone and neuropeptide, acts principally in the hindbrain to decrease food intake and has been recently shown to act as a neurotrophic factor to control the development of AP->NTS and ARC->PVN axonal fiber outgrowth. Amylin is also able to activate ERK signaling specifically in POMC neurons independently of leptin. To investigate the physiological role of amylin signaling in POMC neurons, the core component of the amylin receptor, calcitonin receptor (CTR) was depleted from POMC neurons using an inducible mouse model. The loss of CTR in POMC neurons leads to increased body weight gain, increased adiposity, and glucose intolerance in male knockout mice, characterized by decreased energy expenditure (EE) and decreased expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). Furthermore, a decreased spontaneous locomotor activity and absent thermogenic reaction to the application of the amylin receptor agonist were observed in male and female mice. Together, these results show a significant physiological impact of amylin/calcitonin signaling in CTR-POMC neurons on energy metabolism and demonstrate the need for sex-specific approaches in obesity research and potentially treatment. Full Article
nfl The FKH domain in FOXP3 mRNA frequently contains mutations in hepatocellular carcinoma that influence the subcellular localization and functions of FOXP3 [Molecular Bases of Disease] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC. Full Article
nfl The Histone Methyltransferase MLL1 Directs Macrophage-Mediated Inflammation in Wound Healing and Is Altered in a Murine Model of Obesity and Type 2 Diabetes By diabetes.diabetesjournals.org Published On :: 2017-09-01 Andrew S. KimballSep 1, 2017; 66:2459-2471Immunology and Transplantation Full Article
nfl Visceral Fat Adipokine Secretion Is Associated With Systemic Inflammation in Obese Humans By diabetes.diabetesjournals.org Published On :: 2007-04-01 Luigi FontanaApr 1, 2007; 56:1010-1013Metabolism Full Article
nfl Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice By diabetes.diabetesjournals.org Published On :: 2008-06-01 Patrice D. CaniJun 1, 2008; 57:1470-1481Metabolism Full Article
nfl PPARA Polymorphism Influences the Cardiovascular Benefit of Fenofibrate in Type 2 Diabetes: Findings From ACCORD-Lipid By diabetes.diabetesjournals.org Published On :: 2020-04-01 Mario Luca MorieriApr 1, 2020; 69:771-783Genetics/Genomes/Proteomics/Metabolomics Full Article
nfl Low-Grade Systemic Inflammation and the Development of Type 2 Diabetes: The Atherosclerosis Risk in Communities Study By diabetes.diabetesjournals.org Published On :: 2003-07-01 Bruce B. DuncanJul 1, 2003; 52:1799-1805Pathophysiology Full Article
nfl The Protection of Children in Armed Conflict By feedproxy.google.com Published On :: Tue, 25 Jun 2019 18:10:01 +0000 Research Event 25 September 2019 - 5:30pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham HouseJoanne Neenan, Legal Adviser, UK Foreign and Commonwealth OfficeDarren Stewart, Head of Operational Law, UK Army HeadquartersChair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House With more protracted and urbanized conflicts, the character of warfare is changing in a manner that is having a greater impact on children. Aside from physical harm, they face the trauma of family separation and displacement, are vulnerable to sexual abuse and recruitment as soldiers and suffer severe disruption to their education. This event will discuss how international humanitarian law applies to the protection of children. Are offences against children in armed conflict being prosecuted adequately? Are there better ways of ensuring compliance with the law?This meeting is the second in a series of three commemorating the 70th anniversary of the 1949 Geneva Conventions.This event, which is supported by the British Red Cross, will be followed by a drinks reception.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Department/project International Law Programme, The Limits on War and Preserving the Peace Chanu Peiris Programme Manager, International Law +44 (0)20 7314 3686 Email Full Article
nfl Brexit and the UN Security Council: declining British influence? By feedproxy.google.com Published On :: Wed, 06 Nov 2019 09:14:28 +0000 6 November 2019 , Volume 95, Number 6 Jess Gifkins, Samuel Jarvis and Jason Ralph Read online The United Kingdom's decision to leave the European Union has ramifications beyond the UK and the EU. This article analyses the impact of the Brexit referendum on the UK's political capital in the United Nations Security Council; a dimension of Brexit that has received little attention thus far. Drawing on extensive elite interviews we show that the UK has considerable political capital in the Council, where it is seen as one of the most effective actors, but the reputational costs of Brexit are tarnishing this image. With case-studies on the UK's role in Somalia and Yemen we show how the UK has been able to further its interests with dual roles in the EU and Security Council, and the risks posed by tensions between trade and human rights after Brexit. We also analyse what it takes to be influential within the Security Council and argue that more attention should be paid to the practices of diplomacy. Influence is gained via penholding, strong diplomatic skill and a well-regarded UN permanent representative. The UK accrues political capital as a leader on the humanitarian and human rights side of the Council's agenda, but this reputation is at risk as it exits the EU. Full Article
nfl ICC’s Influence Can Be Strengthened by Ukraine’s Case By feedproxy.google.com Published On :: Wed, 22 Apr 2020 22:27:35 +0000 22 April 2020 Kateryna Busol Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @KaterynaBusol LinkedIn Second in a two-part series analysing why Ukraine’s attempts at international justice are worth taking - and outlining how the impact goes far beyond just the Russia-Ukraine conflict. Part two examines Ukraine’s appeal to the International Criminal Court (ICC) to seek individual criminal responsibility of the alleged perpetrators of the gravest crimes in occupied Crimea and eastern Ukraine. 2020-04-23-Ukraine-Anniversary-Conflict Marking the Day of The National Flag of Ukraine, a day before celebrations of the anniversary of state independence. Photo by ANATOLII STEPANOV/AFP via Getty Images. The recognition by Ukraine of the jurisdiction of the International Criminal Court (ICC) to consider grave crimes allegedly perpetrated in its territory has led to the ICC Prosecutor’s preliminary examination identifying a wave of alleged war crimes and crimes against humanity.There are claims of persecution, forced conscription, deportation, sham trials, enforced disappearances, and property seizure - in Crimea. As well as killings, torture, inhuman treatment, sexual violence, and indiscriminate shelling - in Donbas. The court now needs to decide whether to open a full investigation which could lead to charges against specific individuals, as in the trial currently taking place in the Netherlands over MH-17.However, the ICC does remain a court of last resort as Ukraine retains the principal power to prosecute grave violations perpetrated in its eastern regions and Crimea, with the court only stepping in if Ukraine (or another court with jurisdiction) is either unwilling or unable to do so.As the evidence mounts up, Ukrainian investigators, prosecutors and judges are becoming more open to cooperation with foreign experts, law firms, human rights NGOs and younger domestic professionals - a significant proportion of whom are women.Transformation shows determinationThis is an unusual shift, given the rigid hierarchical nature of post-Soviet institutions, with elderly males in most of the top positions. The transformation shows the determination to see perpetrators of crimes in Crimea and Donbas tried by the ICC, with joint professional development trainings and joint communications about the alleged crimes.Ukraine has also been strengthening its institutions. The Prosecutor’s Office of the Autonomous Republic of Crimea has been improving quality control of its war crime proceedings, and has taken a strong pro-ICC stance. The Office of the Prosecutor General established a special department to monitor the armed conflict proceedings, and two specialised war crime units have been formed in Donbas.Although too early to assess progress - given recent prosecution reform and that much-needed legislation on international crimes is still pending – these are promising signs of Ukraine’s intent to take a specialised approach to armed conflict violations. And Ukrainian civil society organisations are also playing a more important role, documenting alleged crimes and sending evidence to the ICC.Any intervention by the ICC in Ukraine also has a considerable impact on the wider dynamics of addressing international crimes, further extending the court’s reach beyond a focus on Africa which has attracted widespread criticism since it began in 2002.The ICC has already opened investigations in Georgia, Bangladesh/Myanmar, and Afghanistan, with preliminary examinations in Colombia, Venezuela, Iraq/UK, Palestine, and The Philippines. But the Ukrainian case would further develop the European subtleties of the court’s jurisprudence.Although the ICC is currently investigating the 2008 Russia-Georgia war, the active phase of that armed conflict lasted for just five days whereas Russia’s military involvement in Ukraine has been ongoing for the six years. The temporal difference in no way diminishes the suffering of victims and the necessity for the proper investigation, prosecution and compensation in the Georgian context.And yet, going by even the preliminary findings of the ICC prosecutor, the spectrum of war crimes and crimes against humanity allegedly perpetrated in Ukraine is much wider. Some incidents, such as the illegal construction of the Crimean Bridge, is an amalgam of the violations against property, cultural heritage and the environment. Cumulatively, the Ukrainian and Georgian cases would substantially contribute to the development of the court’s emerging European lenses.The Russia-Ukraine armed conflict is also the first instance of armed hostilities of such magnitude and duration in Europe since World War II and the Yugoslav Wars. The ICC’s readiness to take on such geopolitically challenging cases which leave itself open to attack will be tested.But by examining new contexts - including Ukraine - the ICC would develop a more layered reading of the nature and scope of the crimes it works on. For example, alleged indoctrination and use of children by armed groups in eastern Ukraine is likely to differ from the known practices of abducting and recruiting child soldiers in Africa.Investigating evidence of Russia’s persecution of pro-Ukrainian activists - forcing them out of Crimea - coupled with the creation of favourable conditions for Russian citizens to relocate to Crimea could lead to proving the existence of a policy of mass colonisation of the peninsula - adding new layers to the court’s jurisprudence on population displacement. And previously under-prosecuted crimes may come to the fore, such as attacks on cultural property or causing the destruction of the environment.Although the ICC proceedings on Ukraine – along with those being held by the International Court of Justice (ICJ) - are unlikely to bring immediate results, Ukraine has developed an international adjudication strategy based on the available viable options and what can be practically delivered.The simple act of a reputed international court outlining Russia’s alleged violations in Crimea and Donbas and naming those individually responsible would be an impactful achievement in itself, regardless of whether Russia pays any attention or compensation.And any international judgments or those of domestic courts such as the Dutch MH-17 proceedings and Russia’s response - predicted to be non-compliance - is an important argument for continuing sanctions against Russia over its conduct in Ukraine.The mutually reinforcing effect of both the Crimea and Donbas proceedings within Ukraine and at international courts should not be underestimated. These investigations into war crimes, terrorism and human rights issues are deeply relevant - not only for the conflict itself, but also for the development of international law.Part One of this series assesses Ukraine’s efforts to hold Russia accountable as a state at the International Court of Justice (ICJ). Full Article
nfl Cow’s milk allergy guidelines are not evidence based and are beset by conflicts of interest, researchers warn By feeds.bmj.com Published On :: Wednesday, May 6, 2020 - 16:26 Full Article
nfl Screening Room: Parts of a Circle - History of the Karabakh Conflict By feedproxy.google.com Published On :: Tue, 21 Jan 2020 15:55:01 +0000 Members Event 18 February 2020 - 6:00pm to 8:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Jenny Norton, Producer, Parts of a Circle: History of the Karabakh ConflictFamil Ismayilov, JournalistLeon Aslanov, Middle East Analyst, Integrity UKChair: Laurence Broers, Associate Fellow, Russia and Eurasia Programme, Chatham House; Director, Caucasus Programme, Conciliation Resources Once an autonomous region populated mainly by Armenians in Soviet Azerbaijan, Nagorny Karabakh, is a contested territory in the Caucasus. Since the late 1980s, its contested status has driven popular mobilization among Armenians and Azerbaijanis and an all-out war between 1992-94. After a quarter-century of enmity and military build-up, in 2019, Armenian and Azerbaijani leaders agreed to ‘prepare their populations for peace’ but how would this work in practice?Parts of a Circle: History of the Karabakh Conflict (2019) chronicles the disputed history of the decades-old conflict between Armenians and Azerbaijanis. Supported by the European Union and based on a series of three documentary films jointly produced over four years by Armenian and Azerbaijani production teams, the film showcases journalistic cooperation in bridging societies in conflict.The screening was followed by a panel discussion that will explore the state of the conflict and the efforts to end it. Why have efforts to resolve the conflict between Azerbaijan and Armenia not been successful? How can both sides build grassroot support for peace after years of fomenting hatred? And what can the international community do in support?A short film about the making of the documentary can be seen here. Members Events Team Email Full Article
nfl ICC’s Influence Can Be Strengthened by Ukraine’s Case By feedproxy.google.com Published On :: Wed, 22 Apr 2020 22:27:35 +0000 22 April 2020 Kateryna Busol Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @KaterynaBusol LinkedIn Second in a two-part series analysing why Ukraine’s attempts at international justice are worth taking - and outlining how the impact goes far beyond just the Russia-Ukraine conflict. Part two examines Ukraine’s appeal to the International Criminal Court (ICC) to seek individual criminal responsibility of the alleged perpetrators of the gravest crimes in occupied Crimea and eastern Ukraine. 2020-04-23-Ukraine-Anniversary-Conflict Marking the Day of The National Flag of Ukraine, a day before celebrations of the anniversary of state independence. Photo by ANATOLII STEPANOV/AFP via Getty Images. The recognition by Ukraine of the jurisdiction of the International Criminal Court (ICC) to consider grave crimes allegedly perpetrated in its territory has led to the ICC Prosecutor’s preliminary examination identifying a wave of alleged war crimes and crimes against humanity.There are claims of persecution, forced conscription, deportation, sham trials, enforced disappearances, and property seizure - in Crimea. As well as killings, torture, inhuman treatment, sexual violence, and indiscriminate shelling - in Donbas. The court now needs to decide whether to open a full investigation which could lead to charges against specific individuals, as in the trial currently taking place in the Netherlands over MH-17.However, the ICC does remain a court of last resort as Ukraine retains the principal power to prosecute grave violations perpetrated in its eastern regions and Crimea, with the court only stepping in if Ukraine (or another court with jurisdiction) is either unwilling or unable to do so.As the evidence mounts up, Ukrainian investigators, prosecutors and judges are becoming more open to cooperation with foreign experts, law firms, human rights NGOs and younger domestic professionals - a significant proportion of whom are women.Transformation shows determinationThis is an unusual shift, given the rigid hierarchical nature of post-Soviet institutions, with elderly males in most of the top positions. The transformation shows the determination to see perpetrators of crimes in Crimea and Donbas tried by the ICC, with joint professional development trainings and joint communications about the alleged crimes.Ukraine has also been strengthening its institutions. The Prosecutor’s Office of the Autonomous Republic of Crimea has been improving quality control of its war crime proceedings, and has taken a strong pro-ICC stance. The Office of the Prosecutor General established a special department to monitor the armed conflict proceedings, and two specialised war crime units have been formed in Donbas.Although too early to assess progress - given recent prosecution reform and that much-needed legislation on international crimes is still pending – these are promising signs of Ukraine’s intent to take a specialised approach to armed conflict violations. And Ukrainian civil society organisations are also playing a more important role, documenting alleged crimes and sending evidence to the ICC.Any intervention by the ICC in Ukraine also has a considerable impact on the wider dynamics of addressing international crimes, further extending the court’s reach beyond a focus on Africa which has attracted widespread criticism since it began in 2002.The ICC has already opened investigations in Georgia, Bangladesh/Myanmar, and Afghanistan, with preliminary examinations in Colombia, Venezuela, Iraq/UK, Palestine, and The Philippines. But the Ukrainian case would further develop the European subtleties of the court’s jurisprudence.Although the ICC is currently investigating the 2008 Russia-Georgia war, the active phase of that armed conflict lasted for just five days whereas Russia’s military involvement in Ukraine has been ongoing for the six years. The temporal difference in no way diminishes the suffering of victims and the necessity for the proper investigation, prosecution and compensation in the Georgian context.And yet, going by even the preliminary findings of the ICC prosecutor, the spectrum of war crimes and crimes against humanity allegedly perpetrated in Ukraine is much wider. Some incidents, such as the illegal construction of the Crimean Bridge, is an amalgam of the violations against property, cultural heritage and the environment. Cumulatively, the Ukrainian and Georgian cases would substantially contribute to the development of the court’s emerging European lenses.The Russia-Ukraine armed conflict is also the first instance of armed hostilities of such magnitude and duration in Europe since World War II and the Yugoslav Wars. The ICC’s readiness to take on such geopolitically challenging cases which leave itself open to attack will be tested.But by examining new contexts - including Ukraine - the ICC would develop a more layered reading of the nature and scope of the crimes it works on. For example, alleged indoctrination and use of children by armed groups in eastern Ukraine is likely to differ from the known practices of abducting and recruiting child soldiers in Africa.Investigating evidence of Russia’s persecution of pro-Ukrainian activists - forcing them out of Crimea - coupled with the creation of favourable conditions for Russian citizens to relocate to Crimea could lead to proving the existence of a policy of mass colonisation of the peninsula - adding new layers to the court’s jurisprudence on population displacement. And previously under-prosecuted crimes may come to the fore, such as attacks on cultural property or causing the destruction of the environment.Although the ICC proceedings on Ukraine – along with those being held by the International Court of Justice (ICJ) - are unlikely to bring immediate results, Ukraine has developed an international adjudication strategy based on the available viable options and what can be practically delivered.The simple act of a reputed international court outlining Russia’s alleged violations in Crimea and Donbas and naming those individually responsible would be an impactful achievement in itself, regardless of whether Russia pays any attention or compensation.And any international judgments or those of domestic courts such as the Dutch MH-17 proceedings and Russia’s response - predicted to be non-compliance - is an important argument for continuing sanctions against Russia over its conduct in Ukraine.The mutually reinforcing effect of both the Crimea and Donbas proceedings within Ukraine and at international courts should not be underestimated. These investigations into war crimes, terrorism and human rights issues are deeply relevant - not only for the conflict itself, but also for the development of international law.Part One of this series assesses Ukraine’s efforts to hold Russia accountable as a state at the International Court of Justice (ICJ). Full Article
nfl Myeloid HMG-CoA Reductase Determines Adipose Tissue Inflammation, Insulin Resistance, and Hepatic Steatosis in Diet-Induced Obese Mice By diabetes.diabetesjournals.org Published On :: 2020-01-20T12:00:25-08:00 Adipose tissue macrophages (ATMs) are involved in the development of insulin resistance in obesity. We have recently shown that myeloid cell–specific reduction of HMG-CoA reductase (Hmgcrm–/m–), which is the rate-limiting enzyme in cholesterol biosynthesis, protects against atherosclerosis by inhibiting macrophage migration in mice. We hypothesized that ATMs are harder to accumulate in Hmgcrm–/m– mice than in control Hmgcrfl/fl mice in the setting of obesity. To test this hypothesis, we fed Hmgcrm–/m– and Hmgcrfl/fl mice a high-fat diet (HFD) for 24 weeks and compared plasma glucose metabolism as well as insulin signaling and histology between the two groups. Myeloid cell–specific reduction of Hmgcr improved glucose tolerance and insulin sensitivity without altering body weight in the HFD-induced obese mice. The improvement was due to a decrease in the number of ATMs. The ATMs were reduced by decreased recruitment of macrophages as a result of their impaired chemotactic activity. These changes were associated with decreased expression of proinflammatory cytokines in adipose tissues. Myeloid cell–specific reduction of Hmgcr also attenuated hepatic steatosis. In conclusion, reducing myeloid HMGCR may be a promising strategy to improve insulin resistance and hepatic steatosis in obesity. Full Article
nfl Rare inflammatory condition affects some children with COVID-19 By jamaica-gleaner.com Published On :: Thu, 07 May 2020 17:11:53 -0500 Dozens of United States children have been hospitalised with a serious inflammatory condition possibly linked with the coronavirus and first seen in Europe. New York authorities announced Wednesday that 64 potential cases had been reported to... Full Article
nfl Fighting inequality, corruption, and conflict - how to improve South Asia's health By feeds.bmj.com Published On :: Tue, 11 Apr 2017 15:29:46 +0000 The BMJ has published a series of articles, taking an in-depth look at health in South Asia. In this collection, authors from India, Pakistan, Nepal, Bangladesh, Sri Lanka, and Afghanistan collaborate to identify evidence-based solutions to shape health policy and interventions, and drive innovations and research in the region. In this podcast,... Full Article
nfl Manflu - are men immunologically inferior? By feeds.bmj.com Published On :: Tue, 12 Dec 2017 16:26:51 +0000 Manflu, the phenomenon that men experience the symptoms of viral illness more than woman, is usually used with derision - but a new review, published in the Christmas edition, is asking - is there a plausible biological basis for this sex difference? Kyle Sue is a clinical assistant professor in family medicine at Memorial University of... Full Article
nfl Inflammatory Cytokines and the Risk to Develop Type 2 Diabetes: Results of the Prospective Population-Based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study By diabetes.diabetesjournals.org Published On :: 2003-03-01 Joachim SprangerMar 1, 2003; 52:812-817Pathophysiology Full Article
nfl Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice By diabetes.diabetesjournals.org Published On :: 2008-06-01 Patrice D. CaniJun 1, 2008; 57:1470-1481Metabolism Full Article
nfl Rare Genetic Variants of Large Effect Influence Risk of Type 1 Diabetes By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:29-07:00 Most replicated genetic determinants for type 1 diabetes are common (minor allele frequency [MAF] >5%). We aimed to identify novel rare or low-frequency (MAF <5%) single nucleotide polymorphisms with large effects on risk of type 1 diabetes. We undertook deep imputation of genotyped data followed by genome-wide association testing and meta-analysis of 9,358 type 1 diabetes case and 15,705 control subjects from 12 European cohorts. Candidate variants were replicated in a separate cohort of 4,329 case and 9,543 control subjects. Our meta-analysis identified 27 independent variants outside the MHC, among which 3 were novel and had MAF <5%. Three of these variants replicated with Preplication < 0.05 and Pcombined < Pdiscovery. In silico analysis prioritized a rare variant at 2q24.3 (rs60587303 [C], MAF 0.5%) within the first intron of STK39, with an effect size comparable with those of common variants in the INS and PTPN22 loci (combined [from the discovery and replication cohorts] estimate of odds ratio [ORcombined] 1.97, 95% CI 1.58–2.47, Pcombined = 2.9 x 10–9). Pharmacological inhibition of Stk39 activity in primary murine T cells augmented effector responses through enhancement of interleukin 2 signaling. These findings provide insight into the genetic architecture of type 1 diabetes and have identified rare variants having a large effect on disease risk. Full Article
nfl PPARA Polymorphism Influences the Cardiovascular Benefit of Fenofibrate in Type 2 Diabetes: Findings From ACCORD-Lipid By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:29-07:00 The cardiovascular benefits of fibrates have been shown to be heterogeneous and to depend on the presence of atherogenic dyslipidemia. We investigated whether genetic variability in the PPARA gene, coding for the pharmacological target of fibrates (PPAR-α), could be used to improve the selection of patients with type 2 diabetes who may derive cardiovascular benefit from addition of this treatment to statins. We identified a common variant at the PPARA locus (rs6008845, C/T) displaying a study-wide significant influence on the effect of fenofibrate on major cardiovascular events (MACE) among 3,065 self-reported white subjects treated with simvastatin and randomized to fenofibrate or placebo in the ACCORD-Lipid trial. T/T homozygotes (36% of participants) experienced a 51% MACE reduction in response to fenofibrate (hazard ratio 0.49; 95% CI 0.34–0.72), whereas no benefit was observed for other genotypes (Pinteraction = 3.7 x 10–4). The rs6008845-by-fenofibrate interaction on MACE was replicated in African Americans from ACCORD (N = 585, P = 0.02) and in external cohorts (ACCORD-BP, ORIGIN, and TRIUMPH, total N = 3059, P = 0.005). Remarkably, rs6008845 T/T homozygotes experienced a cardiovascular benefit from fibrate even in the absence of atherogenic dyslipidemia. Among these individuals, but not among carriers of other genotypes, fenofibrate treatment was associated with lower circulating levels of CCL11—a proinflammatory and atherogenic chemokine also known as eotaxin (P for rs6008845-by-fenofibrate interaction = 0.003). The GTEx data set revealed regulatory functions of rs6008845 on PPARA expression in many tissues. In summary, we have found a common PPARA regulatory variant that influences the cardiovascular effects of fenofibrate and that could be used to identify patients with type 2 diabetes who would derive benefit from fenofibrate treatment, in addition to those with atherogenic dyslipidemia. Full Article
nfl Human conflict and ecosystem services: finding the environmental price of warfare By feedproxy.google.com Published On :: Wed, 02 Jul 2014 10:57:18 +0000 2 July 2014 , Volume 90, Number 4 Robert A. Francis and Krishna Krishnamurthy Full Article
nfl Addressing Resource Conflicts: Working Towards More Effective Resolution of Natural Resource Disputes By feedproxy.google.com Published On :: Tue, 16 Sep 2014 17:15:01 +0000 Invitation Only Research Event 26 June 2014 - 9:00am to 5:00pm Chatham House, London Disputes over resources are a persistent challenge to international peace and security. Natural resources (such as oil, natural gas, minerals, timber and water) are a major source of national income for many countries and, alongside land, are essential to the livelihoods of many millions of people. There is a growing recognition among researchers and decision-makers that in many fragile states disputes over these resources have fed into, and underpinned, violent conflict and instability. Although international engagement in national resource disputes is not always desirable or feasible, where it is necessary and possible to support, supplement (or even substitute) national dispute resolution processes it is important to think through the parameters of such action: Who gets involved? With what financial resources? When does an intervention begin? How do they act? This one-day roundtable will bring together around 30 experts from policy, academia and business to discuss these questions and more.The event will be held under the Chatham House Rule. Attendance is by invitation only. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme, Resources Climate Conflict and Peacebuilding Owen Grafham Manager, Energy, Environment and Resources Programme +44 (0)20 7957 5708 Email Full Article
nfl Resource Development in Fragile and Conflict-Affected States: Can it Promote Peace? By feedproxy.google.com Published On :: Wed, 10 Dec 2014 14:15:02 +0000 Research Event 30 September 2014 - 1:30pm to 4:45pm Chatham House, London The discovery of valuable natural resources such as hydrocarbons or minerals in conflict-affected states or disputed regions can be a double-edged sword. While economic growth may help overcome conflict and consolidate peace, much of the academic literature links the economic, social and environmental impacts of resource development with an increased risk of violent conflict between or within fragile states. Recently however, the role of business in advancing peace has emerged as a topic of increasing discussion in academia and in forums such as the UN Global Compact. Resource development has also become a key objective for donor development strategies in fragile states such as Afghanistan, Somalia and Myanmar, on the assumption that extractive sector development can contribute to stability and security. This event will gather key stakeholders from business and policy to investigate if and where natural resource development has contributed to peace-building, built cooperation among stakeholders or helped to resolve, rather than exacerbate, tensions. If so, it will endeavour to draw out common, replicable lessons of what made these developments successful from a peace-building perspective.The event will be held under the Chatham House Rule. Event attributes Chatham House Rule Department/project Energy, Environment and Resources Programme, Resources Climate Conflict and Peacebuilding Full Article
nfl TSPO Versus P2X7 as a Target for Neuroinflammation: An In Vitro and In Vivo Study By jnm.snmjournals.org Published On :: 2020-04-01T06:00:28-07:00 Neuroinflammation is important in amyotrophic lateral sclerosis (ALS). The P2X7 receptor (P2X7R) is a promising target for neuroinflammation. The objective of this study was to compare 18F-DPA714, a second-generation translocator protein tracer, with 11C-JNJ717, a novel P2X7R tracer, in vitro and in vivo in ALS. Methods: For the in vitro portion of the study, autoradiography with 18F-DPA714 and 11C-JNJ717 was performed on human ALS brain sections in comparison to immunofluorescence with Iba1 and GFAP. For the in vivo portion, 3 male patients with early-stage ALS (59.3 ± 7.2 y old) and 6 healthy volunteers (48.2 ± 16.5 y old, 2 men and 4 women) underwent dynamic PET/MR scanning with 18F-DPA714 and 11C-JNJ717. Volume-of-distribution images were calculated using Logan plots and analyzed on a volume-of-interest basis. Results: Autoradiography showed no difference in 11C-JNJ717 binding but did show increased 18F-DPA714 binding in the motor cortex correlating with Iba1 expression (glial cells). Similar findings were observed in vivo, with a 13% increase in 18F-DPA714 binding in the motor cortex. Conclusion: In symptomatic ALS patients, 18F-DPA714 showed increased signal whereas 11C-JNJ717 was not elevated. Full Article
nfl Multimodality Imaging of Inflammation and Ventricular Remodeling in Pressure-Overload Heart Failure By jnm.snmjournals.org Published On :: 2020-04-01T06:00:28-07:00 Inflammation contributes to ventricular remodeling after myocardial ischemia, but its role in nonischemic heart failure is poorly understood. Local tissue inflammation is difficult to assess serially during pathogenesis. Although 18F-FDG accumulates in inflammatory leukocytes and thus may identify inflammation in the myocardial microenvironment, it remains unclear whether this imaging technique can isolate diffuse leukocytes in pressure-overload heart failure. We aimed to evaluate whether inflammation with 18F-FDG can be serially imaged in the early stages of pressure-overload–induced heart failure and to compare the time course with functional impairment assessed by cardiac MRI. Methods: C57Bl6/N mice underwent transverse aortic constriction (TAC) (n = 22), sham surgery (n = 12), or coronary ligation as an inflammation-positive control (n = 5). MRI assessed ventricular geometry and contractile function at 2 and 8 d after TAC. Immunostaining identified the extent of inflammatory leukocyte infiltration early in pressure overload. 18F-FDG PET scans were acquired at 3 and 7 d after TAC, under ketamine-xylazine anesthesia to suppress cardiomyocyte glucose uptake. Results: Pressure overload evoked rapid left ventricular dilation compared with sham (end-systolic volume, day 2: 40.6 ± 10.2 μL vs. 23.8 ± 1.7 μL, P < 0.001). Contractile function was similarly impaired (ejection fraction, day 2: 40.9% ± 9.7% vs. 59.2% ± 4.4%, P < 0.001). The severity of contractile impairment was proportional to histology-defined myocardial macrophage density on day 8 (r = –0.669, P = 0.010). PET imaging identified significantly higher left ventricular 18F-FDG accumulation in TAC mice than in sham mice on day 3 (10.5 ± 4.1 percentage injected dose [%ID]/g vs. 3.8 ± 0.9 %ID/g, P < 0.001) and on day 7 (7.8 ± 3.7 %ID/g vs. 3.0 ± 0.8 %ID/g, P = 0.006), though the efficiency of cardiomyocyte suppression was variable among TAC mice. The 18F-FDG signal correlated with ejection fraction (r = –0.75, P = 0.01) and ventricular volume (r = 0.75, P < 0.01). Western immunoblotting demonstrated a 60% elevation of myocardial glucose transporter 4 expression in the left ventricle at 8 d after TAC, indicating altered glucose metabolism. Conclusion: TAC induces rapid changes in left ventricular geometry and contractile function, with a parallel modest infiltration of inflammatory macrophages. Metabolic remodeling overshadows inflammatory leukocyte signal using 18F-FDG PET imaging. More selective inflammatory tracers are requisite to identify the diffuse local inflammation in pressure overload. Full Article
nfl How Far Does the European Union’s Influence Extend? By feedproxy.google.com Published On :: Wed, 12 Feb 2020 16:35:01 +0000 Members Event 26 February 2020 - 6:00pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Anu Bradford, Author, The Brussels Effect: How the European Union Rules the World; Henry L. Moses Professor of Law and International Organization, Columbia Law SchoolCreon Butler, Research Director, Trade, Investment & New Governance Models; Director, Global Economy and Finance Programme, Chatham HouseChair: Pepijn Bergsen, Research Fellow, Europe Programme, Chatham House The European Union (EU) is increasingly looking to its regulatory capacity as a foreign policy tool. In areas such as data privacy and chemical safety, the EU’s success in setting policy standards that are replicated globally have helped cement its reputation as a norm-setting power.Despite this success, narratives of decline that focus on the EU’s internal and external challenges – including Brexit, the rise of China and growing Euroscepticism within member states – have dominated popular discussions of the bloc’s viability and authority.The speakers consider the strengths and shortcomings in the EU’s ability to exert global influence focusing particularly on its norm-setting power. Brussels’ primary motivations for setting internal standards and regulations have traditionally been to preserve and strengthen its single market.What, then, explains the attractiveness of these regulations in external markets? How will the departure of one of its largest internal economies affect the EU’s capacity to export its internal regulations globally?And to what extent could the EU benefit from diversifying its avenues of exerting global influence? Members Events Team Email Full Article
nfl Redefining Nepal: Internal Migration in a Post-Conflict, Post-Disaster Society By www.migrationpolicy.org Published On :: Wed, 17 Jun 2015 17:16:02 -0400 Even as Nepal will lean more heavily on its international diaspora to help recover from devastating earthquakes that killed thousands and decimated parts of the country, the disasters have had effects on internal migration. Class and gender dynamics have long driven significant internal flows. This feature article explores migration trends in Nepal, including movement between ecological zones, growing urbanization, and the feminization of an increasingly mobile workforce. Full Article
nfl Glucosamine Use, Inflammation, and Genetic Susceptibility, and Incidence of Type 2 Diabetes: A Prospective Study in UK Biobank By care.diabetesjournals.org Published On :: 2020-03-20T11:50:34-07:00 OBJECTIVE Glucosamine is a widely used supplement typically taken for osteoarthritis and joint pain. Emerging evidence suggests potential links of glucosamine with glucose metabolism, inflammation, and cardiometabolic risk. We prospectively analyzed the association of habitual glucosamine use with risk of type 2 diabetes (T2D) and assessed whether genetic susceptibility and inflammation status might modify the association. RESEARCH DESIGN AND METHODS This study analyzed 404,508 participants from the UK Biobank who were free of diabetes, cancer, or cardiovascular disease at baseline and completed the questionnaire on supplement use. Cox proportional hazards models were used to evaluate the association between habitual use of glucosamine and risk of incident T2D. RESULTS During a median of 8.1 years of follow-up, 7,228 incident cases of T2D were documented. Glucosamine use was associated with a significantly lower risk of T2D (hazard ratio 0.83, 95% CI 0.78–0.89) after adjustment for age, sex, BMI, race, center, Townsend deprivation index, lifestyle factors, history of disease, and other supplement use. This inverse association was more pronounced in participants with a higher blood level of baseline C-reactive protein than in those with a lower level of this inflammation marker (P-interaction = 0.02). A genetic risk score for T2D did not modify this association (P-interaction = 0.99). CONCLUSIONS Our findings indicate that glucosamine use is associated with a lower risk of incident T2D. Full Article