ndi New Research from Columbia Business School Shows Radical Changes in Household Spending Habits During COVID-19 Epidemic By www8.gsb.columbia.edu Published On :: Tue, 28 Apr 2020 18:37:51 +0000 Business Economics and Public Policy Operations Risk Management Tuesday, April 28, 2020 - 14:30 Study provides first real-time view into household consumption during outbreak in U.S., showing an initial sharp increase in key categories, followed by a sharp decrease in overall spending Full Article
ndi Indicators of cancer may also be markers of heart failure By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (Wiley) Heart failure and cancer are conditions with a number of shared characteristics. A new study published in the Journal of Internal Medicine found that in patients with heart failure, several known tumor markers can also be indicators of heart failure severity and progression. Full Article
ndi Understanding the diversity of cancer evolution based on computational simulation By www.eurekalert.org Published On :: Thu, 30 Apr 2020 00:00:00 EDT (The Institute of Medical Science, The University of Tokyo) Understanding the principles of cancer evolution is important in designing a therapeutic strategy. A research group at The Institute of Medical Science, The University of Tokyo (IMSUT) announced a new simulation model that describes various modes of cancer evolution in a unified manner. Full Article
ndi £1.2 million awarded to improve our understanding of the Sun By www.eurekalert.org Published On :: Fri, 01 May 2020 00:00:00 EDT (Northumbria University ) Researchers from Northumbria University have been awarded £1.2m to help advance our understanding of the Sun and its impact on the planets within our solar system. Full Article
ndi Icelandic DNA jigsaw-puzzle brings new knowledge about Neanderthals By www.eurekalert.org Published On :: Thu, 23 Apr 2020 00:00:00 EDT (Aarhus University) An international team of researchers has put together a new image of Neanderthals based on the genes Neanderthals left in the DNA of modern humans when they had children with them about 50,000 years ago. The researchers found the new information by trawling the genomes of more than 27,000 Icelanders. Among other things, they discovered that Neanderthal children had older mothers and younger fathers than the Homo-Sapien children in Africa did at the time. Full Article
ndi Cannibalism helps invading invertebrates survive severe conditions By www.eurekalert.org Published On :: Thu, 07 May 2020 00:00:00 EDT (University of Southern Denmark) Investing in the future: Researchers show how cannibalism among the invasive comb jelly enables adults to survive severe conditions at the edge of their ecological range with implications for the use and evolutionary origins of cannibalism. Full Article
ndi Rapid coronavirus test receives major funding By www.imperial.ac.uk Published On :: Wed, 06 May 2020 15:00:00 +0100 A coronavirus test – which aims to deliver rapid results – has received major funding. Full Article
ndi Sleeter receives funding for historical simulations on diplomacy By www.eurekalert.org Published On :: Fri, 08 May 2020 00:00:00 EDT (George Mason University) Nathan Sleeter, Research Assistant Professor, Roy Rosenzweig Center for History and New Media (RRCHNM), is directing a project in which RRCHNM will create three classroom simulations based on events from the history of diplomacy for secondary education instructors. Full Article
ndi Climate change could reawaken Indian Ocean El Niño By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (University of Texas at Austin) Global warming is approaching a tipping point that during this century could reawaken an ancient climate pattern similar to El Niño in the Indian Ocean, new research led by scientists from the University of Texas at Austin has found. Full Article
ndi Light, sound, action: Extending the life of acoustic waves on microchips By www.eurekalert.org Published On :: Wed, 06 May 2020 00:00:00 EDT (University of Sydney) Data centres and digital information processors are reaching their capacity limits and producing heat. Foundational work here on optical-acoustic microchips opens door to low-heat, low-energy, fast internet. Full Article
ndi Clinical Management of Food-Insecure Individuals With Diabetes By spectrum.diabetesjournals.org Published On :: 2012-02-01 Andrea LópezFeb 1, 2012; 25:14-18From Research to Practice Full Article
ndi Four Theories and a Philosophy: Self-Management Education for Individuals Newly Diagnosed With Type 2 Diabetes By spectrum.diabetesjournals.org Published On :: 2003-04-01 T. Chas SkinnerApr 1, 2003; 16:Lifestyle and Behavior Full Article
ndi New Research Reveals Dramatic Shifts in US Household Spending By www8.gsb.columbia.edu Published On :: Fri, 01 May 2020 00:00:00 -0400 Data from March shows similarities in spending across various demographics. Full Article
ndi Exploring Public International Law and the Rights of Individuals with Chinese Scholars - Part One By feedproxy.google.com Published On :: Mon, 29 Oct 2018 16:37:47 +0000 17 April 2014 As part of a roundtable series, Chatham House and China University of Political Science and Law (CUPL) jointly organized this four-day meeting at Chatham House for international lawyers to discuss a wide range of issues related to 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 China University of Political Science and Law, 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 roundtable had a total of 22 participants, 10 Chinese (from universities and other academic institutions in Beijing and Shanghai) and 12 non-Chinese (from Australia, Germany, the Netherlands, Switzerland, the United Kingdom and the United States).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
ndi 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
ndi 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
ndi Seminal Plasma Proteome as an Indicator of Sperm Dysfunction and Low Sperm Motility By feedproxy.google.com Published On :: 2020-04-20 Yunlei LiApr 20, 2020; 0:RA120.002017v1-mcp.RA120.002017Research Full Article
ndi Arginine in C9ORF72 Dipolypeptides Mediates Promiscuous Proteome Binding and Multiple Modes of Toxicity By feedproxy.google.com Published On :: 2020-04-01 Mona RadwanApr 1, 2020; 19:640-654Research Full Article
ndi Making the most of attending conferences By blogs.ams.org Published On :: Tue, 08 Oct 2019 16:54:02 +0000 In this blog by Julianne Vega, graduate student at University of Kentucky, Julianne tells us how to make the most of attending math conferences. If you are heading to a conference, challenge yourself! Your first conference may not be the … Continue reading → Full Article career advancement General Graduate School Uncategorized Undegraduates
ndi Finding belonging through mentorship By blogs.ams.org Published On :: Fri, 17 Apr 2020 19:45:03 +0000 Guest blog by Stephen McKean On my first day of college, I showed up an hour early to my very first class. The class was Math 2210, multivariable calculus. For some reason, I thought this was the highest math class … Continue reading → Full Article General Going to graduate school Graduate School Outreach Uncategorized Undegraduates
ndi Understanding Cybercrime for Better Policing: Regional and Global Challenges By feedproxy.google.com Published On :: Fri, 24 May 2019 15:25:01 +0000 Research Event 18 June 2019 - 9:00am to 5:30pm Chatham House | 10 St James's Square | London | SW1Y 4LE In recent years, cybercrime has evolved from a niche technological concern into a prominent global issue with substantial preventative and remedial costs for businesses and governments alike. Despite heavy investment in sophisticated cybersecurity measures and the adoption of several legal, organizational and capacity-building measures, cybercrime remains a major threat which is evolving on a daily basis. Today’s cybercrime is more aggressive, more complex, more organized and – importantly – more unpredictable than ever before.The challenges posed by cybercrime are experienced acutely by countries undergoing digital transformations: as the level of connectivity rises, so too does the potential for online theft, fraud and abuse. Cybercrime is pervasive but governments can work to limit its impact by creating a resilient overall economy and robust institution, and appropriately equipping law enforcement and the justice system to navigate its novel challenges.To advance the discourse surrounding these issues, this workshop will assess the current cyber threat landscape and how it is evolving. It will identify the main obstacles encountered by law enforcement, the judiciary and prosecutors in their fight against cybercrime. It will also compare national, regional and global approaches that countries can use to effectively curb cybercrime and tackle its emerging challenges. Department/project International Security Programme Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email Full Article
Calum Inverarity Research Analyst and Coordinator, International Security Department +44 (0) 207 957 5751 Email
ndi Who’s Afraid of Huawei? Understanding the 5G Security Concerns By feedproxy.google.com Published On :: Fri, 06 Sep 2019 09:55:03 +0000 9 September 2019 Emily Taylor Associate Fellow, International Security Programme @etaylaw LinkedIn Emily Taylor examines the controversy around the Chinese tech giant’s mobile broadband equipment and the different approaches taken by Western countries. 2019-09-06-Huawei.jpg Huawei's Ox Horn campus in Dongguan, China. Photo: Getty Images. As countries move towards the fifth generation of mobile broadband, 5G, the United States has been loudly calling out Huawei as a security threat. It has employed alarmist rhetoric and threatened to limit trade and intelligence sharing with close allies that use Huawei in their 5G infrastructure.While some countries such as Australia have adopted a hard line against Huawei, others like the UK have been more circumspect, arguing that the risks of using the firm’s technology can be mitigated without forgoing the benefits.So, who is right, and why have these close allies taken such different approaches?The risksLong-standing concerns relating to Huawei are plausible. There are credible allegations that it has benefitted from stolen intellectual property, and that it could not thrive without a close relationship with the Chinese state.Huawei hotly denies allegations that users are at risk of its technology being used for state espionage, and says it would resist any order to share information with the Chinese government. But there are questions over whether it could really resist China’s stringent domestic legislation, which compels companies to share data with the government. And given China’s track record of using cyberattacks to conduct intellectual property theft, there may be added risks of embedding a Chinese provider into critical communications infrastructure.In addition, China’s rise as a global technological superpower has been boosted by the flow of financial capital through government subsidies, venture and private equity, which reveal murky boundaries between the state and private sector for domestic darlings. Meanwhile, the Belt and Road initiative has seen generous investment by China in technology infrastructure across Africa, South America and Asia.There’s no such thing as a free lunch or a free network – as Sri Lanka discovered when China assumed shares in a strategic port in return for debt forgiveness; or Mexico when a 1% interest loan for its 4G network came on the condition that 80% of the funding was spent with Huawei.Aside from intelligence and geopolitical concerns, the quality of Huawei’s products represents a significant cyber risk, one that has received less attention than it deserves.On top of that, 5G by itself will significantly increase the threat landscape from a cybersecurity perspective. The network layer will be more intelligent and adaptable through the use of software and cloud services. The number of network antennae will increase by a factor of 20, and many will be poorly secured ‘things’; there is no need for a backdoor if you have any number of ‘bug doors’.Finally, the US is threatening to limit intelligence sharing with its closest allies if they adopt Huawei. So why would any country even consider using Huawei in their 5G infrastructure?Different situationsThe truth is that not every country is free to manoeuvre; 5G technology will sit on top of existing mobile infrastructure.Australia and the US can afford to take a hard line: their national infrastructure has been largely Huawei-free since 2012. However, the Chinese firm is deeply embedded in other countries’ existing structures – for example, in the UK, Huawei has provided telecommunications infrastructure since 2005. Even if the UK decided tomorrow to ditch Huawei, it cannot just rip up existing 4G infrastructure. To do so would cost a fortune, risk years of delay in the adoption of 5G and limit competition in 5G provisioning.As a result, the UK has adopted a pragmatic approach resulting from years of oversight and analysis of Huawei equipment, during which it has never found evidence of malicious Chinese state cyber activity through Huawei.At the heart of this process is the Huawei Cyber Security Evaluation Centre, which was founded in 2010 as a confidence-building measure. Originally criticized for ‘effectively policing itself’, as it was run and staffed entirely by Huawei, the governance has now been strengthened, with the National Cyber Security Centre chairing its oversight board.The board’s 2019 report makes grim reading, highlighting ‘serious and system defects in Huawei’s software engineering and cyber security competence’. But it does not accuse the company of serving as a platform for state-sponsored surveillance.Similar evidence-based policy approaches are emerging in other countries like Norway and Italy. They offer flexibility for governments, for example by limiting access to some contract competition through legitimate and transparent means, such as security reviews during procurement. The approaches also raise security concerns (both national and cyber) to a primary issue when awarding contracts – something that was not always done in the past, when price was the key driver.The UK is also stressing the need to manage risk and increase vendor diversity in the ecosystem to avoid single points of failure. A further approach that is beginning to emerge is to draw a line between network ‘core’ and ‘periphery’ components, excluding some providers from the more sensitive ‘core’. The limited rollouts of 5G in the UK so far have adopted multi-provider strategies, and only one has reportedly not included Huawei kit.Managing the risks to cyber security and national security will become more complex in a 5G environment. In global supply chains, bans based on the nationality of the provider offer little assurance. For countries that have already committed to Huawei in the past, and who may not wish to be drawn into an outright trade war with China, these moderate approaches offer a potential way forward. Full Article
ndi Understanding NATO Obligations Under the NPT By feedproxy.google.com Published On :: Fri, 28 Feb 2020 09:50:48 +0000 The objective of the project is to understand Alliance obligations within the framework of nuclear non-proliferation and disarmament treaties. Examining obligations under the Treaty on the Non-Proliferation of Nuclear Weapons (NPT), and exploring new approaches that NATO could adopt to reconcile strategic stability with nuclear disarmament policies which could be introduced at the 2020 NPT Review Conference (RevCon).The project facilitates the reconciliation of different positions in advance of the RevCon by providing a platform for stakeholders to communicate their respective positions and engage in constructive dialogue. Key research findings and contemporary analysis will be disseminated to officials and the policy community.Through dialogue and research, the project aims to reduce polarisation in the nuclear field and consequently lay a foundation for increased collaboration during the discussions. It also provides a unique opportunity for NATO countries to explore specific new approaches, including in relation to identifying and analysing relevant geopolitical conditions for nuclear disarmament measures that will inform their inputs into the RevCon and related policy framework discussions.This project is supported by the Carnegie Corporation of New York. Full Article
ndi Expanding Sino–Maghreb Relations: Morocco and Tunisia By feedproxy.google.com Published On :: Wed, 26 Feb 2020 12:49:01 +0000 26 February 2020 Over the past two decades, China has increased its presence in North Africa in terms of trade and investment. This paper looks at China’s policy within the context of its Africa and Middle East policies to better understand its approach to Morocco and Tunisia. Read online Download PDF Yahia H. Zoubir Senior Professor of International Studies, KEDGE Business School, France and Visiting Fellow, Brookings Doha Center 2020-02-26-Xi-Jinping-King-Mohammed.jpg Chinese President Xi Jinping and King Mohammed VI of Morocco wave during a welcoming ceremony outside the Great Hall of the People in Beijing on 11 May 2016. Photo: Getty Images. SummaryChina’s presence in the Maghreb has increased in recent years, raising concerns among Western powers. China has focused on bilateral relations with these countries while also working within the Forum on China–Africa Cooperation (FOCAC) and the China–Arab States Cooperation Forum (CASCF). However, this engagement has limited strategic value compared to relations China has with Saudi Arabia or the United Arab Emirates.Since the launch of the Belt and Road Initiative (BRI) in 2013, China has shown greater interest in the Maghreb as an entry point to European and African markets. China has pursued commercial relations over political influence in the region. Morocco and Tunisia are still dependent on France, their former colonial power, and the European Union, which exert great political, economic, security and cultural influence over the two countries.The Maghreb countries’ economic relations with China have grown exponentially, with Algeria forming the closest relationship. However, Morocco and Tunisia are keen to attract China’s investment and involvement in major construction and infrastructure projects to boost industrial and economic development. While China’s investments in Morocco and Tunisia remain at a low level, trade relations with both countries have grown steadily. Politically, China’s policy of noninterference in domestic affairs appeals to Maghreb states, which resent Western interference.China’s influence in the Maghreb remains minimal. Its soft power push has struggled to promote advantages of strong relations with China beyond economics. Furthermore, Morocco and Tunisia’s populations have generally scant knowledge about China’s politics and culture. China has tried to address this lack of familiarity through the establishment of Confucius Institutes and other cultural activities. However, language and cultural barriers still impede the development of close relations, compared to those China has with other countries in Africa. Department/project Middle East and North Africa Programme, Economic Transformation in North Africa Full Article
ndi Targeted optical imaging of the glucagon-like peptide 1 receptor using exendin-4-IRDye800CW By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Rationale: The treatment of choice for insulinomas and focal lesions in congenital hyperinsulinism (CHI) is surgery. However, intra-operative detection can be challenging. This could be overcome with intra-operative fluorescence imaging, which provides real-time lesion detection with a high spatial resolution. Here, a novel method for targeted near-infrared (NIR) fluorescence imaging of glucagon-like peptide 1 receptor (GLP-1R) positive lesions, using the GLP-1 agonist exendin-4, labeled with IRDye800CW, was examined in vitro and in vivo. Methods: A competitive binding assay was performed using Chinese hamster lung (CHL) cells transfected with the GLP-1R. Tracer biodistribution was determined in BALB/c nude mice bearing subcutaneous CHL-GLP-1R xenografts. In vivo NIR fluorescence imaging of CHL-GLP-1R xenografts was performed. Localization of the tracer in the pancreatic islets of BALB/c nude mice was examined using fluorescence microscopy. Laparoscopic imaging was performed to detect the fluorescent signal of the tracer in the pancreas of mini pigs. Results: Exendin-4-IRDye800CW binds the GLP-1R with an IC50 value of 3.96 nM. The tracer accumulates in CHL-GLP-1R xenografts. Subcutaneous CHL-GLP-1R xenografts were visualized using in vivo NIR fluorescence imaging. The tracer accumulates specifically in the pancreatic islets of mice and a clear fluorescent signal was detected in the pancreas of mini pigs. Conclusion: These date provide the first in vivo evidence of the feasibility of targeted fluorescence imaging of GLP-1R positive lesions. Intra-operative lesion delineation using exendin-4-IRDye800CW could benefit open as well as laparoscopic surgical procedures for removal of insulinomas and focal lesions in CHI. Full Article
ndi Individual mapping of innate immune cell activation is a candidate marker of patient-specific trajectories of disability worsening in Multiple Sclerosis By jnm.snmjournals.org Published On :: 2020-01-31T13:36:41-08:00 Objective: To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18F-DPA-714 translocator protein (TSPO) positron emission tomography (PET), and to explore the relationship between these maps and individual trajectories of disability worsening in patients with multiple sclerosis (MS). Methods: Patients with MS (n = 37), whose trajectories of disability worsening over the 2 years preceding study entry were calculated, and healthy controls (n = 19) underwent magnetic resonance magnetic and 18F-DPA-714 PET. A threshold of significant activation of 18F-DPA-714 binding was calculated with a voxel-wise randomized permutation-based comparison between patients and controls, and used to classify each WM voxel in patients as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were employed to calculate the extent of activation in WM regions-of-interests and to classify each WM lesion as "DPA-active", "DPA-inactive" or "unclassified". Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM, (NAWM in patients=24.9±9.7%; WM in controls=14.0±7.8%, p<0.001). In patients with MS, the percentage of DPA+ voxels showed a significant increase from NAWM, to perilesional areas, T2 hyperintense lesions and T1 hypointense lesions (38.1±13.5%, 45.0±17.9%, and 51.9±22.9%, respectively, p<0.001). Among the 1379 T2 lesions identified, 512 were defined as DPA-active and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (OR=1.13, P = 0.009), a higher percentage of DPA+ voxels in the NAWM (OR=1.16, P = 0.009) and in T1-spin-echo lesions (OR=1.06, P = 0.036), were significantly associated with a retrospective more severe clinical trajectory in patients with MS. Conclusion: A more severe trajectory of disability worsening in MS is associated with an innate immune cells activation inside and around WM lesions. 18F-DPA-714 PET may provide a promising biomarker to identify patients at risk of severe clinical trajectory. Full Article
ndi NEMESIS: Non-inferiority, Individual Patient Meta-analysis of Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres versus Sorafenib in Advanced Hepatocellular Carcinoma By jnm.snmjournals.org Published On :: 2020-05-01T11:16:57-07:00 In randomized clinical trials (RCTs), no survival benefit has been observed for selective internal radiotherapy (SIRT) over sorafenib in patients with advanced hepatocellular carcinoma (aHCC). This study aimed to assess by means of a meta-analysis whether overall survival (OS) with SIRT, as monotherapy or followed by sorafenib, is non-inferior to sorafenib, and compare safety profiles for patients with aHCC. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library up to February 2019 to identify RCTs comparing SIRT as monotherapy, or followed by sorafenib, to sorafenib monotherapy among patients with aHCC. The main outcomes were OS and frequency of treatment-related severe adverse events (AEs grade ≥3). The per-protocol population was the primary analysis population. A non-inferiority margin of 1.08 in terms of hazard ratio (HR) was pre-specified for the upper boundary of 95% confidence interval (CI) for OS. Pre-specified subgroup analyses were performed. Results: Three RCTs, involving 1,243 patients, comparing sorafenib with SIRT (SIRveNIB and SARAH) or SIRT followed by sorafenib (SORAMIC), were included. After randomization, 411/635 (64.7%) patients allocated to SIRT and 522/608 (85.8%) allocated to sorafenib completed the studies without major protocol deviations. Median OS with SIRT, whether or not followed by sorafenib, was non-inferior to sorafenib (10.2 and 9.2 months, [HR 0.91, 95% CI 0.78–1.05]). Treatment-related severe adverse events were reported in 149/515 patients (28.9%) who received SIRT and 249/575 (43.3%) who received sorafenib only (p<0.01). Conclusion: SIRT as initial therapy for aHCC is non-inferior to sorafenib in terms of OS, and offers a better safety profile. Full Article
ndi 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
ndi The effects of monosodium glutamate on PSMA radiotracer uptake in men with recurrent prostate cancer: a prospective, randomized, double-blind, placebo-controlled intra-individual imaging study. By jnm.snmjournals.org Published On :: 2020-05-08T13:18:58-07:00 The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [18F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [18F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications. Full Article
ndi Understanding South Africa's Political Landscape By feedproxy.google.com Published On :: Mon, 04 Nov 2019 15:55:01 +0000 Members Event 14 November 2019 - 6:00pm to 7:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Carien du Plessis, Journalist; Co-Author, Understanding South AfricaJames Hamill, Associate Fellow, International Institute for Strategic Studies; Author, Africa's Lost Leader: South Africa's Continental Role Since ApartheidMartin Plaut, Senior Researcher, Institute of Commonwealth Studies; Co-Author, Understanding South AfricaChair: Pumela Salela, UK Country Head, Brand South Africa President Cyril Ramaphosa led the African National Congress (ANC) to electoral victory in South Africa in May 2019. His promise of rooting out corruption and generating job-creating growth resonated with an electorate scarred by corruption scandals and structural economic and racial inequality.However, divisions within the ruling party have meant that the delivery of these promises has been slow. Complex and often divisive racial dynamics continue to dominate political discourse especially around land reform and economic transformation.The country’s main opposition party, the Democratic Alliance (DA), faces its own political crisis following the resignation of former leader Mmusi Maimane, bringing into question the role of opposition parties in the young democracy. At this event, South African journalists, Martin Plaut and Carien du Plessis, discuss their new book, Understanding South Africa, providing insights into the current and historical trends that define the political fault lines of modern South Africa. Is Ramaphosa shying away from the difficult political decisions necessary to encourage meaningful change in South Africa’s political environment? And how should the international community understand the trends and dynamics that dominate South African politics? Members Events Team Email Full Article
ndi Africa’s Long-standing Leaders Are Disappearing By feedproxy.google.com Published On :: Fri, 03 Jan 2020 16:07:49 +0000 3 January 2020 Dr Alex Vines OBE Managing Director, Ethics, Risk & Resilience; Director, Africa Programme Leaders who cling to power are being pushed out across the continent, and the trend looks set to continue in 2020. 2020-01-03-Zim.jpg A man holds a portrait of Robert Mugabe during his official funeral ceremony. Photo: Getty Images. Africa’s dinosaur leaders are members of an increasingly small and unstable club. Popular protests last year forced Algeria’s president, Abdelaziz Bouteflika, out of office after almost 20 years in power, as well as Sudan’s president, Omar al-Bashir, who ruled for 30 years. In 2017, Robert Mugabe was deposed in a military coup (although this was denied) after 40 years. And in 2011, mass protests led to the downfall of Tunisia’s president, Zine el-Abidine Ben Ali, after he had been in power for 23 years.Somewhat smoother are the political transitions in Angola and the Democratic Republic of the Congo (DRC). José Eduardo dos Santos, after almost 38 years in power, stepped down from office in 2017 as his term ended. So did his younger neighbour, Joseph Kabila, in January 2019, after 18 years in the presidency.What the six former leaders had in common was that they wanted to remain heads of state and considered succession planning or stepping down only as a last resort. This year will be crucial for the six countries in political transition particularly as the reform-window period is short.From A to Z Algeria: Tens of thousands of protesters have rallied in the capital Algiers and other cities against the December 2019 elections, rejecting what they see as sham transitional politics. A soft landing for Algeria in 2020 is unlikely, and what happens in the year has significant regional implications.Angola: A transition is under way, led by President João Lourenço. This shift is smoother than many others, but 2020 will be the watershed year. The country has been in economic recession for four years but is predicted to see gross domestic product growth in 2020. Investment and job creation will determine the pace of change. The honeymoon period has ended and there are signs of increasing frustration among the urban youth and the middle class.DRC: Despite his constitutionally mandated term expiring in December 2016, Joseph Kabila continued his presidency by continuously postponing elections until 30 December 2018. This election saw a three-way contest between the Union for Democracy and Social Progress (UDSP), the Engagement for Citizenship and Development party and the People’s Party for Reconstruction and Democracy (PPRD). Fèlix Tshisekedi of the UDSP was declared the winner by the Independent National Electoral Commission on January 10 last year with 38.6% votes. He was followed by Martin Fayulu of the Engagement for Citizenship and Development party, with 34.8%. He denounced the election results. In third place was Emmanuel Ramazani Shadary, of the PPRD, a key ally of Kabila.Although this was the first peaceful transition of power in DRC, there were widespread electoral inconsistencies and some observers believed that Fayulu was the legitimate winner. In 2020 it will become clearer whether a genuine transition from Kabila’s influence is taking place.Sudan: More promising than the DRC or Algeria, a 39-month transitional administration led by a technocratic prime minister, Abdalla Hamdok, has been established and enjoys domestic and international goodwill. This honeymoon is likely to be short, and the transitional administration needs to show results. The United States can help by removing Sudan from its terror list, thereby lifting the de facto ban on Sudan’s access to the dollar-based international financial system.Tunisia: A low-profile, conservative law professor beat a charismatic media magnate released from prison in the presidential election runoff in October 2019. Kais Saied won 70% of the vote and his victory and the putting together of a new governing coalition is another step forward in an open-ended democratic transition that started in 2011 after Ben Ali fell.Zimbabwe: This is a deeply troubled transition with an acute foreign exchange liquidity crisis, a deteriorating economy, hyperinflation and underperforming government. The state’s clinics and hospitals are closed or turn away patients as medical supplies run out and the doctors’ strike over decimated wages continues. There are power outages and almost half of the people face hunger and starvation as a result of drought and the economic crisis.Zimbabwe’s 2020 looks bleak, a far cry from the euphoria of two years ago when a “military assisted transition” removed Mugabe and replaced him with Emmerson Mnangagwa.More changes comingSo what do these political developments in 2019 tell us more broadly?Long-standing leaders have been persistent in Africa, despite the end of single-party rule in favour of a multiparty system. About a fifth of all African heads of state since independence can be classed as long-standing leaders — in power for more than a decade — and only five countries have never experienced one. But the trend is in decline.It remains most resilient in central Africa and in the Great Lakes regions. Cracks are appearing in their citadels in Malabo and Kampala, but in 2019 Equatorial Guinea’s President Teodoro Obiang Mbasogo celebrated 40 years in power and Uganda’s Yoweri Museveni 33 years.Will there be any more departures from the dinosaurs club in 2020?One of the shortest serving members of this club, President Pierre Nkurunziza (14 years in power) has said he will not stand for the 2020 elections in Burundi, although this is uncertain given that a 2018 constitutional referendum could allow him to stay in power until 2034. Togo’s Faure Gnassingbé (14 years in power) will stand for re-election to the presidency again after Parliament in 2019 approved a constitutional change permitting him to potentially stay in office until 2030.Amending constitutions to change term limits so that incumbent leaders can run for office is a favoured tactic. Rwanda’s Paul Kagame (19 years in office) and the Republic of Congo’s Denis Sassou Nguesso (25 years in power) have done this. But Eritrea’s Isaias Afwerki has never held an election during his 16 years in power.Attempts at dynasties have been less successful, such as with Grace Mugabe in Zimbabwe or Gamal Mubarak in Egypt, but Obiang is grooming his playboy son Teodorin to succeed him and Gabon’s Ali Bongo and Togo’s Gnassingbé both succeeded their fathers.The year is a reminder that more of these long-standing leaders will, in 2020 and beyond, step down or die. Most long-standing leaders in Africa are over the age of 70, with Paul Biya, aged 86, having served 37 years as Cameroon’s president.Some former leaders capitulated under internal pressure: in Algeria, Sudan, Tunisia and Zimbabwe. Only in Angola and the DRC was a transition process organized as part of an elite bargain.What the political transitions have in common is that honeymoons are short and that, whether they are led by interim administrations or elected leaders, they need to deliver political and socioeconomic improvements to succeed, but have inherited shambolic economies. Their success depends on accountable political leadership and domestic and international support.This article was originally published by the Mail & Guardian. Full Article
ndi Innovative Funding for Humanitarian Impact in Africa By feedproxy.google.com Published On :: Fri, 24 Jan 2020 11:00:02 +0000 Research Event 3 February 2020 - 5:00pm to 6:15pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Helen Alderson, Head of Regional Delegation to UK and Ireland, International Committee of the Red CrossPaul van Zyl, Co-Founder and Chief Creative Officer, The ConduitMaya Marissa Malek, Chief Executive Officer, Amanie Advisors Global OfficeChair: Maram Ahmed, Senior Teaching Fellow, SOAS, University of London The cost of humanitarian assistance is forecast to rise to $50 billion per year by 2030 as a result of long-running, complex conflicts as well as natural disasters. Requirements are particularly acute in fragile contexts in sub-Saharan Africa that have lacked the fiscal and technical capacity for crisis prevention and response. As a result, traditional humanitarian actors are increasingly collaborating with the private sector and utilizing tools such as impact bonds, faith-based finance and other innovative financial products and services to mobilize greater funding to address humanitarian needs.At this event, a panel of speakers will assess the challenges for sustainable financing in the humanitarian sector and prospects for multi-stakeholder collaboration and innovative funding tools to fill the widening deficit in assistance needs.THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED. Department/project Africa Programme, African Peace and Security Sahar Eljack Programme Administrator, Africa Programme + 44 (0) 20 7314 3660 Email Full Article
ndi The Central African Republic: Security, Development and Responding to the Humanitarian Situation By feedproxy.google.com Published On :: Fri, 24 Jan 2020 11:00:02 +0000 Invitation Only Research Event 3 February 2020 - 2:00pm to 3:00pm Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Denise Brown, United Nations Deputy Special Representative of the Secretary-General, Resident and Humanitarian Coordinator in the Central African RepublicChair: Ben Shepherd, Consulting Fellow, Africa Programme, Chatham House With two-thirds of the country’s population estimated to be in need of humanitarian aid and one-quarter either internally displaced or living as refugees in neighbouring countries, the Central African Republic (CAR) continues to face serious and complex humanitarian challenges. The country’s forthcoming presidential elections scheduled for December 2020 risk inflaming CAR’s volatile security situation particularly with the return of former leader, François Bozizé, ousted by the Séléka rebel coalition leader, Michel Djotodia, who has also returned from exile.At this event, Denise Brown will discuss CAR’s current security, humanitarian and development situations and the role of actors such as the United Nations Multidimensional Integrated Stabilization Mission in the Central African Republic (MINUSCA). She will also discuss prospects for much-needed governance reform and reconciliation.Attendance at this event is by invitation only. Event attributes Chatham House Rule Department/project Africa Programme, Elections and political systems, Central and East Africa Hanna Desta Programme Assistant, Africa Programme Email Full Article
ndi Beyond Lockdown: Africa’s Options for Responding to COVID-19 By feedproxy.google.com Published On :: Tue, 21 Apr 2020 15:42:52 +0000 21 April 2020 Ben Shepherd Consulting Fellow, Africa Programme Nina van der Mark Research Analyst, Global Health Programme @vdm_nina LinkedIn The continent’s enormous diversity means that there will be no one African experience of COVID-19, nor a uniform governmental response. But there are some common challenges across the continent, and a chance to get the response right. 2020-04-22-Africa-COVID-Dakar Dakar after the Interior Ministry announced compulsory wearing of masks in public and private services, shops and transport, under penalty of sanctions. Photo by SEYLLOU/AFP via Getty Images. African policymakers face a dilemma when it comes to COVID-19. The first hope is to prevent the virus from gaining a foothold at all, and many African states have significant experience of managing infectious disease outbreaks. The establishment of the Africa Centre for Disease Control highlights the hugely increased focus on public health in recent years.But capacities to track, test and isolate vary wildly, notably between neighbours with porous and poorly controlled borders and, in most cases, sustained national-level disease control is difficult. Initial clusters of COVID-19 cases are already established in many places, but a lack of testing capacity makes it hard to know the full extent of transmission.It is not obvious what African states should do as a response. Lack of information about COVID-19 means the proportion of asymptomatic or mild cases is not known, still less the ways in which this is influenced by human geography and demographics.Africa is an overwhelmingly young continent with a median age under 20. But it also faces chronic malnutrition, which may weaken immune responses, and infectious diseases such as malaria, TB and HIV are widespread which could worsen the impact of COVID-19, particularly if treatment for these diseases is interrupted.Complex and unknownUltimately, how all these factors interact with COVID-19 is complex and remains largely unknown. Africa may escape with a relatively light toll. Or it could be hit harder than anywhere else.What is clear, however, is that cost of simply following the rest of the world into lockdown could be high. Africa is relatively rural but has higher populations living in informal settlements than anywhere in the world. Many live in cramped and overcrowded accommodation without clean water or reliable electricity, making handwashing a challenge and working from home impossible.And the benefits appear limited. The goal of lockdowns in most places is not to eliminate the virus but to accept the economic and social costs as a price worth paying in order to ‘flatten the curve’ of infection and protect healthcare systems from being overwhelmed. But this logic does not hold when many of Africa’s healthcare systems are barely coping with pre-coronavirus levels of disease.Africa suffers in comparison to much of the rest of the world in terms of access to quality and affordable healthcare, critical care beds and specialist personnel. For example, in 2017, Nigeria had just 120 ICU beds for a country of 200 million, equating to 0.07 per 100,000 inhabitants compared to 12.5 per 100,000 in Italy and 3.6 per 100,000 in China.The pandemic’s ruinous economic impacts could also be more acute for Africa than anywhere else. The continent is highly vulnerable to potential drops in output and relies heavily on demand from China and Europe. Many states are already facing sharply falling natural resource revenues, and investment, tourism and remittances will suffer - all on top of a high existing debt burden.Analysis by the World Bank shows that Africa will likely face its first recession in 25 years, with the continental economy contracting by up to 5.1% in 2020. Africa will have scant financial ammunition to use in the fight against COVID-19 with currencies weakening, food prices rising, local agri-food supply chains disrupted and food imports likely to decrease as well. A food security emergency appears a strong possibility.So, although several states have imposed national lockdowns and others closed major urban centres, lockdowns are difficult to manage and sustain, especially in places where the daily hustle of the informal sector or subsistence agriculture are the only means of survival and where the state has neither the trust of the population nor the capacity to replace lost earnings or meet basic needs.Of course, this is not simply a binary choice between lockdown or no lockdown - a range of intermediate options exist, such as some restriction on movement, curfews, shutting places of worship, banning only large gatherings, or closing pubs, schools and borders.A significant number of African states have so far taken this middle path. This will not prevent the virus from spreading nor, in all probability, be enough to ensure adequate healthcare for all Africans infected with COVID-19. But it may help slow the spread and buy invaluable time for African states and partners to prepare.How this time is used is therefore of paramount importance. Popular trust in the state is low in many African countries so strategies must empower communities, not alienate them. Africa’s experience of previous epidemics and long traditions of collective resilience and community-based crisis response - which persist in many places – are significant strengths.The right messages must be carried by the right messengers, and policies - including cash transfers and food distribution - implemented sensitively. If not, or if responses become militarized, public consent is unlikely to be sustained for long. Full Article
ndi Site-specific N-glycan Analysis of Antibody-binding Fc {gamma} Receptors from Primary Human Monocytes [Research] By feedproxy.google.com Published On :: 2020-02-01T00:05:30-08:00 FcRIIIa (CD16a) and FcRIIa (CD32a) on monocytes are essential for proper effector functions including antibody dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Indeed, therapeutic monoclonal antibodies (mAbs) that bind FcRs with greater affinity exhibit greater efficacy. Furthermore, post-translational modification impacts antibody binding affinity, most notably the composition of the asparagine(N)-linked glycan at N162 of CD16a. CD16a is widely recognized as the key receptor for the monocyte response, however the post-translational modifications of CD16a from endogenous monocytes are not described. Here we isolated monocytes from individual donors and characterized the composition of CD16a and CD32a N-glycans from all modified sites. The composition of CD16a N-glycans varied by glycosylation site and donor. CD16a displayed primarily complex-type biantennary N-glycans at N162, however some individuals expressed CD16a V158 with ~20% hybrid and oligomannose types which increased affinity for IgG1 Fc according to surface plasmon resonance binding analyses. The CD16a N45-glycans contain markedly less processing than other sites with >75% hybrid and oligomannose forms. N38 and N74 of CD16a both contain highly processed complex-type N-glycans with N-acetyllactosamine repeats and complex-type biantennary N-glycans dominate at N169. The composition of CD16a N-glycans isolated from monocytes included a higher proportion of oligomannose-type N-glycans at N45 and less sialylation plus greater branch fucosylation than we observed in a recent analysis of NK cell CD16a. The additional analysis of CD32a from monocytes revealed different features than observed for CD16a including the presence of a predominantly biantennary complex-type N-glycans with two sialic acids at both sites (N64 and N145). Full Article
ndi Advances in Tools to Determine the Glycan-Binding Specificities of Lectins and Antibodies [Reviews] By feedproxy.google.com Published On :: 2020-02-01T00:05:29-08:00 Proteins that bind carbohydrate structures can serve as tools to quantify or localize specific glycans in biological specimens. Such proteins, including lectins and glycan-binding antibodies, are particularly valuable if accurate information is available about the glycans that a protein binds. Glycan arrays have been transformational for uncovering rich information about the nuances and complexities of glycan-binding specificity. A challenge, however, has been the analysis of the data. Because protein-glycan interactions are so complex, simplistic modes of analyzing the data and describing glycan-binding specificities have proven inadequate in many cases. This review surveys the methods for handling high-content data on protein-glycan interactions. We contrast the approaches that have been demonstrated and provide an overview of the resources that are available. We also give an outlook on the promising experimental technologies for generating new insights into protein-glycan interactions, as well as a perspective on the limitations that currently face the field. Full Article
ndi Arginine in C9ORF72 Dipolypeptides Mediates Promiscuous Proteome Binding and Multiple Modes of Toxicity [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 C9ORF72-associated Motor Neuron Disease patients feature abnormal expression of 5 dipeptide repeat (DPR) polymers. Here we used quantitative proteomics in a mouse neuronal-like cell line (Neuro2a) to demonstrate that the Arg residues in the most toxic DPRS, PR and GR, leads to a promiscuous binding to the proteome compared with a relative sparse binding of the more inert AP and GA. Notable targets included ribosomal proteins, translation initiation factors and translation elongation factors. PR and GR comprising more than 10 repeats appeared to robustly stall on ribosomes during translation suggesting Arg-rich peptide domains can electrostatically jam the ribosome exit tunnel during synthesis. Poly-GR also recruited arginine methylases, induced hypomethylation of endogenous proteins, and induced a profound destabilization of the actin cytoskeleton. Our findings point to arginine in GR and PR polymers as multivalent toxins to translation as well as arginine methylation that may explain the dysfunction of biological processes including ribosome biogenesis, mRNA splicing and cytoskeleton assembly. Full Article
ndi Understanding China’s Evolving Role in Global Economic Governance By feedproxy.google.com Published On :: Mon, 04 Nov 2019 13:00:01 +0000 Invitation Only Research Event 21 November 2019 - 4:00pm to 22 November 2019 - 5:00pm The Hague, The Netherlands Draft Agendapdf | 130.1 KB Almost four years since it was established, the China-led Asian Infrastructure Investment Bank (AIIB) has approved 49 projects and proposed 28. The AIIB claims to be more efficient and less bureaucratic than traditional multilateral development banks (MDB’s) which has threatened the existing model of multilateral development finance. At the same time, China’s increased role in previously Western-led economic institutions, such as the WTO and IMF, has raised questions over the future of the international trade order. How will a rising China shape the international institutional order? Where are there opportunities for potential collaboration and what areas pose challenges? And how should other states and international organizations respond?Attendance at this event is by invitation only. Department/project Asia-Pacific Programme, Geopolitics and Governance, Trade, Investment and Economics Lucy Ridout Programme Administrator, Asia-Pacific Programme +44 (0) 207 314 2761 Email Full Article
ndi Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells By feedproxy.google.com Published On :: 2020-04-01 Kotaro HamaApr 1, 2020; 61:523-536Patient-Oriented and Epidemiological Research Full Article
ndi Episode 51 - The Internet of Sick Burns (IoSB) Snapchat IPO, Android Wear 2.0 and Apple in India By play.acast.com Published On :: Fri, 10 Feb 2017 11:20:46 GMT Techworld Editor Charlotte Jee conducts the tech orchestra this week, trying to get a tune out of this cold, creaking week. Online Editor at Computerworld UK Scott Carey lets us know all about Snapchat's upcoming IPO, billions of dollars, and the gang comes to the realisation they'll perhaps never understand what it's for. Then Senior Staff Writer at PC Advisor Henry Burrell recaps on Google and LG's launch of Android Wear 2.0 and ask - frankly - is it a big deal? Finally Acting Editor at Macworld UK David Price discusses Apple's rumoured plans to move manufacturing to India, which inevitably moves us on to Tech Trumps. See acast.com/privacy for privacy and opt-out information. Full Article tech technology snapchat pod podcast IPO Google Android Wear 2.0 smartwatches Apple Donald Trump
ndi WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding Protein And Its Related Proteins [Thematic Reviews] By feedproxy.google.com Published On :: 2018-10-15T08:42:37-07:00 This article has been withdrawn by the authors as part of this review overlapped with the contents of Pietrangelo A and Ridgway ND. 2018. Cellular and Molecular Life Sciences. 75; 3079-98. Full Article
ndi WHO Can Do Better - But Halting Funding is No Answer By feedproxy.google.com Published On :: Mon, 20 Apr 2020 09:11:18 +0000 20 April 2020 Dr Charles Clift Senior Consulting Fellow, Global Health Programme @CliftWorks Calling a halt to funding for an unspecified time is an unsatisfactory halfway house for the World Health Organization (WHO) to deal with. But with Congress and several US agencies heavily involved, whether a halt is even feasible is under question. 2020-04-20-PPE-Ethiopia-WHO Checking boxes of personal protective equipment (PPE) at the Bole International Airport in Addis Ababa, Ethiopia. Photo by SAMUEL HABTAB/AFP via Getty Images. Donald Trump is impulsive. His sudden decision to stop funding the World Health Organization (WHO) just days after calling it 'very China-centric” and 'wrong about a lot of things' is the latest example. And this in the midst of the worst pandemic since Spanish flu in 1918 and a looming economic crisis compared by some to the 1930s. But the decision is not really just about what WHO might or might not have done wrong. It is more about the ongoing geopolitical wrangle between the US and China, and about diverting attention from US failings in its own response to coronavirus in the run-up to the US presidential election.It clearly also derives from Trump’s deep antipathy to almost any multilateral organization. WHO has been chosen as the fall guy in this political maelstrom in a way that might please Trump’s supporters who will have read or heard little about WHO’s role in tackling this crisis. And the decision has been widely condemned in almost all other countries and by many in the US.What is it likely to mean in practice for WHO?Calling a halt to funding for an unspecified time is an unsatisfactory halfway house. A so-called factsheet put out by the White House talks about the reforms it thinks necessary 'before the organization can be trusted again'. This rather implies that the US wants to remain a member of WHO if it can achieve the changes it wants. Whether those changes are feasible is another question — they include holding member states accountable for accurate data-sharing and countering what is referred to as 'China’s outsize influence on the organization'. Trump said the funding halt would last while WHO’s mismanagement of the coronavirus pandemic was investigated, which would take 60-90 days. The US is the single largest funder of WHO, providing about 16% of its budget. It provides funds to WHO in two ways. The first is the assessed contribution — the subscription each country pays to be a member. In 2018/19 the US contribution should have been $237 million but, as of January this year it was in arrears by about $200 million.Much bigger are US voluntary contributions provided to WHO for specified activities amounting in the same period to another $650 million. These are for a wide variety of projects — more than one-quarter goes to polio eradication, but a significant portion also is for WHO’s emergency work. The US assessed contribution represents only 4% of WHO’s budget. Losing that would certainly be a blow to WHO but a manageable one. Given the arrears situation it is not certain that the US would have paid any of this in the next three months in any case. More serious would be losing the US voluntary contributions which account for about another 12% of WHO’s budget—but whether this could be halted all at once is very unclear. First Congress allocates funds in the US, not the president, raising questions about how a halt could be engineered domestically.Secondly, US contributions to WHO come from about ten different US government agencies, such as the National Institutes of Health or USAID, each of whom have separate agreements with WHO. Will they be prepared to cut funding for ongoing projects with WHO? And does the US want to disrupt ongoing programmes such as polio eradication and, indeed, emergency response which contribute to saving lives? Given the president’s ability to do 180 degree U-turns we shall have to wait and see what will actually happen in the medium term. If it presages the US leaving WHO, this would only facilitate growing Chinese influence in the WHO and other UN bodies. Perhaps in the end wiser advice will be heeded and a viable solution found.Most of President Trump’s criticisms of WHO do not bear close scrutiny. WHO may have made mistakes — it may have given too much credence to information coming from the Chinese. China has just announced that the death toll in Wuhan was 50% higher than previously revealed. It may have overpraised China’s performance and system, but this was part of a deliberate strategy to secure China’s active collaboration so that it could help other countries learn from China’s experience. The chief message from this sorry story is that two countries are using WHO as a pawn in pursuing their respective political agendas which encompass issues well beyond the pandemic. China has been very successful in gaining WHO’s seal of approval, in spite of concerns about events prior to it declaring the problem to the WHO and the world. This, in turn, has invited retaliation from the US. When this is over will be the time to learn lessons about what WHO should have done better. But China, the US, and the global community of nations also need to consider their own responsibility in contributing to this terrible unfolding tragedy.This article was originally published in the British Medical Journal Full Article
ndi Beyond Lockdown: Africa’s Options for Responding to COVID-19 By feedproxy.google.com Published On :: Tue, 21 Apr 2020 15:42:52 +0000 21 April 2020 Ben Shepherd Consulting Fellow, Africa Programme Nina van der Mark Research Analyst, Global Health Programme @vdm_nina LinkedIn The continent’s enormous diversity means that there will be no one African experience of COVID-19, nor a uniform governmental response. But there are some common challenges across the continent, and a chance to get the response right. 2020-04-22-Africa-COVID-Dakar Dakar after the Interior Ministry announced compulsory wearing of masks in public and private services, shops and transport, under penalty of sanctions. Photo by SEYLLOU/AFP via Getty Images. African policymakers face a dilemma when it comes to COVID-19. The first hope is to prevent the virus from gaining a foothold at all, and many African states have significant experience of managing infectious disease outbreaks. The establishment of the Africa Centre for Disease Control highlights the hugely increased focus on public health in recent years.But capacities to track, test and isolate vary wildly, notably between neighbours with porous and poorly controlled borders and, in most cases, sustained national-level disease control is difficult. Initial clusters of COVID-19 cases are already established in many places, but a lack of testing capacity makes it hard to know the full extent of transmission.It is not obvious what African states should do as a response. Lack of information about COVID-19 means the proportion of asymptomatic or mild cases is not known, still less the ways in which this is influenced by human geography and demographics.Africa is an overwhelmingly young continent with a median age under 20. But it also faces chronic malnutrition, which may weaken immune responses, and infectious diseases such as malaria, TB and HIV are widespread which could worsen the impact of COVID-19, particularly if treatment for these diseases is interrupted.Complex and unknownUltimately, how all these factors interact with COVID-19 is complex and remains largely unknown. Africa may escape with a relatively light toll. Or it could be hit harder than anywhere else.What is clear, however, is that cost of simply following the rest of the world into lockdown could be high. Africa is relatively rural but has higher populations living in informal settlements than anywhere in the world. Many live in cramped and overcrowded accommodation without clean water or reliable electricity, making handwashing a challenge and working from home impossible.And the benefits appear limited. The goal of lockdowns in most places is not to eliminate the virus but to accept the economic and social costs as a price worth paying in order to ‘flatten the curve’ of infection and protect healthcare systems from being overwhelmed. But this logic does not hold when many of Africa’s healthcare systems are barely coping with pre-coronavirus levels of disease.Africa suffers in comparison to much of the rest of the world in terms of access to quality and affordable healthcare, critical care beds and specialist personnel. For example, in 2017, Nigeria had just 120 ICU beds for a country of 200 million, equating to 0.07 per 100,000 inhabitants compared to 12.5 per 100,000 in Italy and 3.6 per 100,000 in China.The pandemic’s ruinous economic impacts could also be more acute for Africa than anywhere else. The continent is highly vulnerable to potential drops in output and relies heavily on demand from China and Europe. Many states are already facing sharply falling natural resource revenues, and investment, tourism and remittances will suffer - all on top of a high existing debt burden.Analysis by the World Bank shows that Africa will likely face its first recession in 25 years, with the continental economy contracting by up to 5.1% in 2020. Africa will have scant financial ammunition to use in the fight against COVID-19 with currencies weakening, food prices rising, local agri-food supply chains disrupted and food imports likely to decrease as well. A food security emergency appears a strong possibility.So, although several states have imposed national lockdowns and others closed major urban centres, lockdowns are difficult to manage and sustain, especially in places where the daily hustle of the informal sector or subsistence agriculture are the only means of survival and where the state has neither the trust of the population nor the capacity to replace lost earnings or meet basic needs.Of course, this is not simply a binary choice between lockdown or no lockdown - a range of intermediate options exist, such as some restriction on movement, curfews, shutting places of worship, banning only large gatherings, or closing pubs, schools and borders.A significant number of African states have so far taken this middle path. This will not prevent the virus from spreading nor, in all probability, be enough to ensure adequate healthcare for all Africans infected with COVID-19. But it may help slow the spread and buy invaluable time for African states and partners to prepare.How this time is used is therefore of paramount importance. Popular trust in the state is low in many African countries so strategies must empower communities, not alienate them. Africa’s experience of previous epidemics and long traditions of collective resilience and community-based crisis response - which persist in many places – are significant strengths.The right messages must be carried by the right messengers, and policies - including cash transfers and food distribution - implemented sensitively. If not, or if responses become militarized, public consent is unlikely to be sustained for long. Full Article
ndi Seminal Plasma Proteome as an Indicator of Sperm Dysfunction and Low Sperm Motility [Research] By feedproxy.google.com Published On :: 2020-04-20T08:36:49-07:00 Molecular mechanisms underlying sperm motility have not been fully explained, particularly in chickens. The objective was to identify seminal plasma proteins associated with chicken sperm motility by comparing the seminal plasma proteomic profile of roosters with low sperm motility (LSM, n = 4) and high sperm motility (HSM, n = 4). Using a label-free MS-based method, a total of 522 seminal plasma proteins were identified, including 386 (~74%) previously reported and 136 novel ones. A total of 70 differentially abundant proteins were defined, including 48 more-abundant, 15 less-abundant, and seven proteins unique to the LSM group (specific proteins). Key secretory proteins like less-abundant ADGRG2 and more-abundant SPINK2 in the LSM suggested that the corresponding secretory tissues played a crucial role in maintaining sperm motility. Majority (80%) of the more-abundant and five specific proteins were annotated to the cytoplasmic domain which might be a result of higher plasma membrane damage and acrosome dysfunction in LSM. Additionally, more-abundant mitochondrial proteins were detected in LSM seminal plasma associated with lower spermatozoa mitochondrial membrane potential (m) and ATP concentrations. Further studies showed that the spermatozoa might be suffering from oxidative stress, as the amount of spermatozoa reactive oxygen species (ROS) were largely enhanced, seminal malondialdehyde (MDA) concentrations were increased, and the seminal plasma total antioxidant capacity (T-AOC) were decreased. Our study provides an additional catalog of chicken seminal plasma proteome and supports the idea that seminal plasma could be as an indicator of spermatozoa physiology. More-abundant of acrosome, mitochondria and sperm cytoskeleton proteins in the seminal plasma could be a marker of sperm dysfunction and loss of motility. The degeneration of spermatozoa caused the reduced seminal T-AOC and enhanced oxidative stress might be potential determinants of low sperm motility. These results could extend our understanding of sperm motility and sperm physiology regulation. Full Article
ndi Separation of postprandial lipoproteins: improved purification of chylomicrons using an ApoB100 immunoaffinity method [Methods] By feedproxy.google.com Published On :: 2020-03-01T00:06:33-08:00 Elevated levels of triglyceride-rich lipoproteins (TRLs), both fasting and postprandial, are associated with increased risk for atherosclerosis. However, guidelines for treatment are defined solely by fasting lipid levels, even though postprandial lipids may be more informative. In the postprandial state, circulating lipids consist of dietary fat transported from the intestine in chylomicrons (CMs; containing ApoB48) and fat transported from the liver in VLDL (containing ApoB100). Research into the roles of endogenous versus dietary fat has been hindered because of the difficulty in separating these particles by ultracentrifugation. CM fractions have considerable contamination from VLDL (purity, 10%). To separate CMs from VLDL, we produced polyclonal antibodies against ApoB100 and generated immunoaffinity columns. TRLs isolated by ultracentrifugation of plasma were applied to these columns, and highly purified CMs were collected (purity, 90–94%). Overall eight healthy unmedicated adult volunteers (BMI, 27.2 ± 1.4 kg/m2; fasting triacylglycerol, 102.6 ± 19.5 mg/dl) participated in a feeding study, which contained an oral stable-isotope tracer (1-13C acetate). We then used this technique on plasma samples freshly collected during an 8 h human feeding study from a subset of four subjects. We analyzed fractionated lipoproteins by Western blot, isolated and derivatized triacylglycerols, and calculated fractional de novo lipogenesis. The results demonstrated effective separation of postprandial lipoproteins and substantially improved purity compared with ultracentrifugation protocols, using the immunoaffinity method. This method can be used to better delineate the role of dietary sugar and fat on postprandial lipids in cardiovascular risk and explore the potential role of CM remnants in atherosclerosis. Full Article
ndi Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells [Patient-Oriented and Epidemiological Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:29-07:00 X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder caused by deleterious mutations in the ABCD1 gene. The ABCD1 protein transports very long-chain FAs (VLCFAs) from the cytosol into the peroxisome where the VLCFAs are degraded through β-oxidation. ABCD1 dysfunction leads to VLCFA accumulation in individuals with X-ALD. FAs are activated by esterification to CoA before metabolic utilization. However, the intracellular pools and metabolic profiles of individual acyl-CoA esters have not been fully analyzed. In this study, we profiled the acyl-CoA species in fibroblasts from X-ALD patients and in ABCD1-deficient HeLa cells. We found that hexacosenoyl (26:1)-CoA, but not hexacosanoyl (26:0)-CoA, was the most abundantly concentrated among the VLCFA-CoA species in these cells. We also show that 26:1-CoA is mainly synthesized from oleoyl-CoA, and the metabolic turnover rate of 26:1-CoA was almost identical to that of oleoyl-CoA in both WT and ABCD1-deficient HeLa cells. The findings of our study provide precise quantitative and metabolic information of each acyl-CoA species in living cells. Our results suggest that VLCFA is endogenously synthesized as VLCFA-CoA through a FA elongation pathway and is then efficiently converted to other metabolites, such as phospholipids, in the absence of ABCD1. Full Article
ndi Problem Notes for SAS®9 - 65904: SAS Federation Server stops responding when you run queries against X_OBJECT_PRIVILEGES in SYSCAT and the queries run for hours By feedproxy.google.com Published On :: Fri, 1 May 2020 14:48:24 EST The select * from "SYSCAT"."SYSCAT"."X_EFFECTIVE_OBJECT_PRIVILEGES" query runs for hours. In this scenario, SAS Federation Server stops responding, making it unavailable for use. Restarting SAS Federation Server solves t Full Article DFFEDSVR+SAS+Federation+Server
ndi The Metabolic Responses to 24-h Fasting and Mild Cold Exposure in Overweight Individuals are Correlated and Accompanied by Changes in FGF21 Concentration By diabetes.diabetesjournals.org Published On :: 2020-04-27T16:35:54-07:00 A greater decrease in 24-h energy expenditure (24EE) during 24h fasting defines a thriftier metabolic phenotype prone to weight gain during overfeeding and resistant to weight loss during caloric restriction. As the thermogenic response to mild cold exposure (COLD) may similarly characterize this human phenotype identified by acute fasting conditions, we analyzed changes in 24EE and sleeping metabolic rate (SLEEP) in a whole-room indirect calorimeter during 24h fasting at thermoneutrality (24°C) and during energy balance both at thermoneutrality (24°C) and mild cold (19°C) in 20 healthy volunteers (80% male, age: 36.6±11.4y, percentage body fat: 34.8±10.5%). Greater decrease in 24EE during fasting (thriftier phenotype) was associated with less increase in 24EE during COLD, i.e. less cold-induced thermogenesis. Greater decreases in plasma fibroblast growth factor 21 (FGF21) after 24h fasting and after COLD were highly correlated and associated with greater decreases in SLEEP in both conditions. We conclude that the metabolic responses to short-term fasting and COLD are associated and mediated by the liver-derived hormone FGF21. Thus, the 24EE response to COLD further identifies the thrifty versus spendthrift phenotype, providing an additional setting to investigate the physiological mechanisms underlying the human metabolic phenotype and characterizing the individual susceptibility to weight change. Full Article
ndi Circulating Protein Signatures and Causal Candidates for Type 2 Diabetes By diabetes.diabetesjournals.org Published On :: 2020-05-08T10:11:46-07:00 The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bi-directional two-sample Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes. Full Article
ndi Stress-Induced Translational Regulation Mediated by RNA Binding Proteins: Key Links to {beta}-Cell Failure in Diabetes By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 In type 2 diabetes, β-cells endure various forms of cellular stress, including oxidative stress and endoplasmic reticulum stress, secondary to increased demand for insulin production and extracellular perturbations, including hyperglycemia. Chronic exposure to stress causes impaired insulin secretion, apoptosis, and loss of cell identity, and a combination of these processes leads to β-cell failure and severe hyperglycemia. Therefore, a better understanding of the molecular mechanisms underlying stress responses in β-cells promises to reveal new therapeutic opportunities for type 2 diabetes. In this perspective, we discuss posttranscriptional control of gene expression as a critical, but underappreciated, layer of regulation with broad importance during stress responses. Specifically, regulation of mRNA translation occurs pervasively during stress to activate gene expression programs; however, the convenience of RNA sequencing has caused translational regulation to be overlooked compared with transcriptional controls. We highlight the role of RNA binding proteins in shaping selective translational regulation during stress and the mechanisms underlying this level of regulation. A growing body of evidence indicates that RNA binding proteins control an array of processes in β-cells, including the synthesis and secretion of insulin. Therefore, systematic evaluations of translational regulation and the upstream factors shaping this level of regulation are critical areas of investigation to expand our understanding of β-cell failure in type 2 diabetes. Full Article