Sylwia Struk
Dec 28, 2020; 0:RA119.001766v1-mcp.RA119.001766
Research

Martin Prescher
Dec 1, 2020; 61:1605-1616
Research Articles

Prabuddha Dey
Dec 1, 2020; 61:1556-1564
Reviews

Thibaut Bourgeois
Dec 11, 2020; 0:jlr.RA120000737v1-jlr.RA120000737
Research Articles

In SAS Customer Intelligence Studio, you can choose to create a new calculated variable in the Edit Value dialog box when you populate a treatment custom detail. Following creation of the new calculated

Editing and/or saving an action column can take up to a minute to display a window. There are no workarounds identified at this time.

In SAS Life Science Analytics Framework 4.6, group membership removal fails with an exception if a user is set as assignee, a candidate, or a notification recipient in a user task for a Process Flow . The Process

Certain tables that are created in SAS Scalable Performance Data (SPD) Server might not be displayed correctly by SAS Federation Server Manager. Tables that have Latin5 characters in column names encounter this

Recent studies have highlighted an important role for lysophosphatidylcholine acyltransferase 3 (LPCAT3) in controlling the PUFA composition of cell membranes in the liver and intestine. In these organs, LPCAT3 critically supports cell membrane-associated processes such as lipid absorption or lipoprotein secretion. However, the role of LPCAT3 in macrophages remains controversial. Here, we investigated LPCAT3’s role in macrophages both in vitro and in vivo in mice with atherosclerosis and obesity. To accomplish this, we used the LysMCre strategy to develop a mouse model with conditional Lpcat3 deficiency in myeloid cells (Lpcat3KOMac). We observed that partial Lpcat3 deficiency (approx. 75% reduction) in macrophages alters the PUFA composition of all phospholipid (PL) subclasses, including phosphatidylinositols and phosphatidylserines. A reduced incorporation of C20 PUFAs (mainly arachidonic acid [AA]) into PLs was associated with a redistribution of these FAs toward other cellular lipids such as cholesteryl esters. Lpcat3 deficiency had no obvious impact on macrophage inflammatory response or endoplasmic reticulum (ER) stress; however, Lpcat3KOMac macrophages exhibited a reduction in cholesterol efflux in vitro. In vivo, myeloid Lpcat3 deficiency did not affect atherosclerosis development in LDL receptor deficient mouse (Ldlr-/-) mice. Lpcat3KOMac mice on a high-fat diet displayed a mild increase in hepatic steatosis associated with alterations in several liver metabolic pathways and in liver eicosanoid composition. We conclude that alterations in AA metabolism along with myeloid Lpcat3 deficiency may secondarily affect AA homeostasis in the whole liver, leading to metabolic disorders and triglyceride accumulation.

ABCB4/MDR3 is located in the canalicular membrane of hepatocytes and translocates PC-lipids from the cytoplasmic to the extracellular leaflet. ABCB4 is an ATP-dependent transporter that reduces the harsh detergent effect of the bile salts by counteracting self-digestion. To do so, ABCB4 provides PC lipids for extraction into bile. PC lipids account for 40% of the entire pool of lipids in the canalicular membrane with an unknown distribution over both leaflets. Extracted PC lipids end up in so-called mixed micelles. Mixed micelles are composed of phospholipids, bile salts, and cholesterol. Ninety to ninety-five percent of the phospholipids are members of the PC family, but only a subset of mainly 16.0-18:1 PC and 16:0-18:2 PC variants are present. To elucidate whether ABCB4 is the key discriminator in this enrichment of specific PC lipids, we used in vitro studies to identify crucial determinants in substrate selection. We demonstrate that PC-lipid moieties alone are insufficient for stimulating ABCB4 ATPase activity, and that at least two acyl chains and the backbone itself are required for a productive interaction. The nature of the fatty acids, like length or saturation has a quantitative impact on the ATPase activity. Our data demonstrate a two-step enrichment and protective function of ABCB4 to mitigate the harsh detergent effect of the bile salts, because ABCB4 can translocate more than just the PC-lipid variants found in bile.

Phosphatidate phosphatase (PAP) catalyzes the penultimate step in the synthesis of triacylglycerol and regulates the synthesis of membrane phospholipids. There is much interest in this enzyme because it controls the cellular levels of its substrate, phosphatidate (PA), and product, DAG; defects in the metabolism of these lipid intermediates are the basis for lipid-based diseases such as obesity, lipodystrophy, and inflammation. The measurement of PAP activity is required for studies aimed at understanding its mechanisms of action, how it is regulated, and for screening its activators and/or inhibitors. Enzyme activity is determined through the use of radioactive and nonradioactive assays that measure the product, DAG, or P_i. However, sensitivity and ease of use are variable across these methods. This review summarizes approaches to synthesize radioactive PA, to analyze radioactive and nonradioactive products, DAG and P_i, and discusses the advantages and disadvantages of each PAP assay.

α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson's disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for α-Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of α-Syn in these mechanisms is currently unclear. Here we investigate the associations of α-Syn with the acidic phosphoinositides (PIPs), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2). Our results show that α-Syn colocalizes with PIP2 and the phosphorylated active form of the clathrin adaptor protein 2 (AP2) at clathrin-coated pits. Using endocytosis of transferrin as an indicator for clathrin-mediated endocytosis (CME), we find that α-Syn involvement in endocytosis is specifically mediated through PI(4,5)P2 levels on the plasma membrane. In accord with their effects on PI(4,5)P2 levels, the PD associated A30P, E46K, and A53T mutations in α-Syn further enhance CME in neuronal and nonneuronal cells. However, lysine to glutamic acid substitutions at the KTKEGV repeat domain of α-Syn, which interfere with phospholipid binding, are ineffective in enhancing CME. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by the α-Syn mutations and associates with their effects on PI(4,5)P2 levels, however, with the exception of the A30P mutation. This study provides evidence for a critical involvement of PIPs in α-Syn–mediated membrane trafficking.

Insulin receptor substrate 2 (IRS2) is an essential adaptor that mediates signaling downstream of the insulin receptor and other receptor tyrosine kinases. Transduction through IRS2-dependent pathways is important for coordinating metabolic homeostasis, and dysregulation of IRS2 causes systemic insulin signaling defects. Despite the importance of maintaining proper IRS2 abundance, little is known about what factors mediate its protein stability. We conducted an unbiased proteomic screen to uncover novel substrates of the Anaphase Promoting Complex/Cyclosome (APC/C), a ubiquitin ligase that controls the abundance of key cell cycle regulators. We found that IRS2 levels are regulated by APC/C activity and that IRS2 is a direct APC/C target in G₁. Consistent with the APC/C's role in degrading cell cycle regulators, quantitative proteomic analysis of IRS2-null cells revealed a deficiency in proteins involved in cell cycle progression. We further show that cells lacking IRS2 display a weakened spindle assembly checkpoint in cells treated with microtubule inhibitors. Together, these findings reveal a new pathway for IRS2 turnover and indicate that IRS2 is a component of the cell cycle control system in addition to acting as an essential metabolic regulator.

The neuronal basis of complex social behavior is still poorly understood. In honeybees, reproductive investment decisions are made at the colony-level. Queens develop from female-destined larvae that receive alloparental care from nurse bees in the form of ad-libitum royal jelly (RJ) secretions. Typically, the number of raised new queens is limited but genetic breeding of "royal jelly bees" (RJBs) for enhanced RJ production over decades has led to a dramatic increase of reproductive investment in queens. Here, we compare RJBs to unselected Italian bees (ITBs) to investigate how their cognitive processing of larval signals in the mushroom bodies (MBs) and antennal lobes (ALs) may contribute to their behavioral differences. A cross-fostering experiment confirms that the RJB syndrome is mainly due to a shift in nurse bee alloparental care behavior. Using olfactory conditioning of the proboscis extension reflex, we show that the RJB nurses spontaneously respond more often to larval odors compared with ITB nurses but their subsequent learning occurs at similar rates. These phenotypic findings are corroborated by our demonstration that the proteome of the brain, particularly of the ALs differs between RJBs and ITBs. Notably, in the ALs of RJB newly emerged bees and nurses compared with ITBs, processes of energy and nutrient metabolism, signal transduction are up-regulated, priming the ALs for receiving and processing the brood signals from the antennae. Moreover, highly abundant major royal jelly proteins and hexamerins in RJBs compared with ITBs during early life when the nervous system still develops suggest crucial new neurobiological roles for these well-characterized proteins. Altogether, our findings reveal that RJBs have evolved a strong olfactory response to larvae, enabled by numerous neurophysiological adaptations that increase the nurse bees' alloparental care behavior.

The F-box protein MORE AXILLARY GROWTH 2 (MAX2) is a central component in the signaling cascade of strigolactones (SLs) as well as of the smoke derived karrikins (KARs) and the so far unknown endogenous KAI2 ligand (KL). The two groups of molecules are involved in overlapping and unique developmental processes, and signal-specific outcomes are attributed to perception by the paralogous α/β-hydrolases DWARF14 (D14) for SL and KARRIKIN INSENSITIVE 2/ HYPOSENSITIVE TO LIGHT (KAI2/HTL) for KAR/KL. Additionally, depending on which receptor is activated, specific members of the SUPPRESSOR OF MAX2 1 (SMAX1) – LIKE (SMXL) family control KAR/KL and SL responses. As proteins that function in the same signal transduction pathway often occur in large protein complexes, we aimed at discovering new players of the MAX2, D14 and KAI2 protein network by tandem affinity purification using Arabidopsis cell cultures. When using MAX2 as a bait, various proteins were co-purified among which general components of the Skp1-Cullin-F-box complex and members of the CONSTITUTIVE PHOTOMORPHOGENIC 9 signalosome. Here, we report the identification of a novel interactor of MAX2, a type 5 serine/threonine protein phosphatase, designated PHYTOCHROME-ASSOCIATED PROTEIN PHOSPHATASE 5 (PAPP5). Quantitative affinity purification pointed at PAPP5 as being more present in KAI2 rather than D14 protein complexes. In agreement, mutant analysis suggests that PAPP5 modulates KAR/KL-dependent seed germination in suboptimal conditions and seedling development. Additionally, a phosphopeptide enrichment experiment revealed that PAPP5 might dephosphorylate MAX2 in vivo independently of the synthetic strigolactone analog, rac-GR24. Together, by analyzing the protein complexes to which MAX2, D14 and KAI2 belong, we revealed a new MAX2 interactor, PAPP5, that might act through dephosphorylation of MAX2 to control mainly KAR/KL- related phenotypes and, hence, provide another link with the light pathway.

Moscow Rules: What Drives Russia to Confront the West Book sysadmin 17 January 2019

Keir Giles surveys Russia’s history and the present day to explain why its current leadership feels it has no choice but to challenge and attack the West. Recognising and accepting that this will not change in the near future will help the West find a way of dealing with Russia without risking a deeper conflict.

This book is for anyone that cannot understand why Russia and its leaders behave as they do.

The relationship between Russia and the West is once again deep in crisis. A major reason is that Western leaders have too often believed or hoped that Russia sees the world as they do — but things look very different from Moscow. This book shows that efforts at engagement with Russia that do not take this into account are a key reason for repeated disappointment and crisis.

In confronting the West, Russia is implementing strategic and doctrinal approaches that have been consistent for centuries. The roots of current Russian behaviour and demands can be traced not just to the Soviet era, but back into Tsarist foreign and domestic policy, and further to the structure and rules of Russian society. But this also gives the US and the West pointers for how to behave — and how not to — in order to manage the challenge of Russia effectively, based on past experience of both successful and unsuccessful engagement with Moscow.

The book recognizes the reality of confrontation and provides an essential introduction to grasping why Russia sees it as inevitable. Consequently, it offers a basis for building a less crisis-prone relationship with Russia.

This book is part of the Insights series.

Praise for Moscow Rules

About the author

Keir Giles is a senior consulting fellow at Chatham House, the Royal Institute of International Affairs. He also works with the Conflict Studies Research Centre (CSRC), a group of subject matter experts in Eurasian security with a particular focus on the wide range of security challenges coming from Russia.

Purchase

• UK (via Amazon)
• Rest of world (via Brookings Institution Press)
• Students (via Browns Books)

The Chatham House Sustainable Laboratories Initiative: Prior Assessment Tool Other resource sysadmin 14 June 2019

Laboratories are critical for supporting effective infectious disease surveillance and outbreak response. This tool is meant to help structure a conversation between funding partners and recipient countries on how to most effectively establish or repurpose laboratories in low-resource environments.

Introduction

Laboratories are critical for supporting effective infectious disease surveillance and outbreak response, and lack of adequate laboratory capacity is a global challenge. As part of global health security initiatives, cooperative threat reduction efforts and international development programmes, sophisticated laboratories have been provided to mitigate biological threats and bolster a country’s capacity for detection, diagnosis and storage of high-consequence pathogens. Very often, these use the assumptions, standards and templates applied in high-income countries. However, it can be difficult or even impossible to sustain these facilities in low-resource environments. There can sometimes be limited local technical capacity and capability, which can result in a high reliance on imported expertise, skills, equipment and other resources. Sustainability can therefore be hard to achieve. In addition, when a funding partner withdraws, the laboratories can become disused, foundering without the trained personnel and financial resources to sustain them.

To help address this situation, a proposal gaining increasing support internationally is to adopt an approach based on a local risk assessment, whereby laboratories are appropriately and optimally tailored to the local risks and to the resources available, both in the short and longer term, without compromising biosafety and biosecurity.

A Chatham House workshop was convened in Abuja, Nigeria, in 2018 to explore what West African countries would find most appropriate in terms of building laboratory capacity, what the main challenges have been so far, and what needs to be done to improve the sustainability of laboratories in the region. It emerged that there was a need for a more structured conversation between the funding partner and recipient country early in the process – prior to embarking on the detailed planning phase for the establishment or repurposing of a laboratory. This should involve careful consideration and an assessment of existing and planned capacity, needs and contextual issues, together with proposals for how to address the issues revealed, so that any ensuing laboratory demonstrably supports the national strategy and therefore flourishes.

COP26: What happened, what does this mean, and what happens next? Chatham House briefing NCapeling 15 November 2021

Analysing a crucial opportunity for enhancing ambitions on climate finance, adaptation, and ‘loss and damage’, and the implementation of the Paris Agreement.

Key findings

Raising the ambition of national emission reduction targets (nationally determined contributions – NDCs) was a critical task for COP26. On this front, governments fell short: although over 120 parties have submitted new or updated NDCs, the new targets only narrow the gap to 1.5°C by 15–17 per cent, and are, if fully implemented (and this is far from certain), projected to result in warming of 2.4°C by the end of the century.

If warming is to be limited to 1.5°C above pre-industrial levels, additional emissions reductions before 2030, over and above current NDC pledges, will need to equate to reducing emissions by the equivalent of two years of current annual emissions. To keep warming to 2°C, the equivalent reductions would be needed of one year’s total emissions.

The Glasgow Climate Pact – the main political outcome of COP26 – requests governments to revisit and strengthen their NDCs before the end of 2022 to bring these in line with the Paris Agreement’s temperature goal. To keep 1.5°C within reach, it will be absolutely essential that governments return to the table with significantly enhanced offers ahead of COP27, which will take place at Sharm El-Sheikh, Egypt, in 2022.

Another key feature of the Glasgow Climate Pact is the reference to ‘accelerating efforts towards the phasedown of unabated coal power and phase-out of inefficient fossil fuel subsidies’. Although the language was watered down over the course of the negotiations, COP26 marks the first time ever reducing fossil fuels is mentioned in a COP decision.

Discussions around climate finance, adaptation, and loss and damage were centre stage in Glasgow, and were critical points of contention. Although the Glasgow Climate Pact urges developed countries to ‘fully’ deliver on the $100 billion annual climate finance pledge through to 2025, it remains unclear when this sum will actually be raised in full – and if a total of $500 billion will be mobilized between 2020 and 2025 to make up for initial shortfalls.

And while the Pact urges developed countries to double their adaptation finance by 2025, and establishes a dialogue on loss and damage finance, much more will need to be done to address the needs of climate-vulnerable developing countries. 

COP26 saw a flurry of plurilateral deals on key issues such as phasing out various forms of fossil fuels and ending deforestation. These initiatives have the potential to accelerate decarbonization, but monitoring their implementation and holding governments and other institutions to account will be critical. Future COPs provide a platform for doing this, and governments should seek to incorporate the pledges made outside the formal remits of the UNFCCC process in their NDCs.

While some progress was made at COP26, the next 12 months will be crucial in determining if the formal agreements reached in Glasgow provide grounds for optimism that 1.5°C remains firmly in sight, and are sufficient to build trust between countries and between citizens and governments.

Read the full analysis

Chatham House Primer: Inside China’s government 30 November 2022 — 6:00PM TO 6:45PM Anonymous (not verified) 4 October 2022 Chatham House

How are decisions made in Beijing, across China and where does the CCP fit in?

Still little is known in Western circles about the inner workings of China’s government. In power since 1949, the ruling Chinese Communist Party has evolved over decades to its current embodiment under President Xi Jinping.

The need for a better understanding of China’s government has been heightened, particularly as the country navigates post-COVID troubles, global economic downturns, wars in Europe, climate change and heightened tension with the United States.

This Primer has been prepared to pull back the veil on the Chinese government. Key issues to be tackled include:

• What is the decision-making process in China’s government?

• How is the party–government relationship best explained?

• How has the party evolved in recent years with new forms of governance and leadership?

• How has China’s government evolved in recent years, particularly in a globalized environment?

• A description of the central government–province dynamic?

• How are citizens engaged in the political process?

• What are the major centres of power in the Chinese political system?

• Has the COVID-19 pandemic altered attitudes towards and the operation of government?

As with all Chatham House member events, questions from members drive the conversation.

What’s next in UK monetary policy? 4 November 2022 — 4:00PM TO 5:30PM Anonymous (not verified) 19 October 2022 Chatham House and Online

A panel of leading experts discuss the future direction of UK monetary policy.

The UK’s so-called ‘mini-budget’ on 23 September led to a severe market reaction and a wave of criticism at home and abroad that ultimately forced the sacking of UK chancellor Kwasi Kwarteng and contributed to the downfall of Liz Truss’s government.

The new chancellor Jeremy Hunt is due to deliver what will essentially be an entirely new budget in mid-November, with a full assessment from the Office of Budget Responsibility. This will follow the meeting of the Bank of England’s interest rate setting Monetary Policy Committee (MPC) on Thursday 3 November.

Given rising inflationary pressures worldwide, it seems highly likely that the MPC will increase interest rates once again, but by how much and how far there will have to be an additional premium linked to the government’s fiscal strategy is far from clear.

Chatham House’s Global Economy and Finance programme is pleased to partner with Fathom Consulting to host a special session of Fathom’s Monetary Policy Forum.

A presentation of Fathom’s latest economic outlook, fully updated to take account of the previous day’s MPC decision, will be followed by a discussion among four of the MPC’s original former external members. Key questions will include:

• How far has the government been able to restore its fiscal credibility?
• Did the MPC make the right decision on 3 November?
• What is the likely pace and extent of monetary tightening in the UK going forward?
• What will be the long-term consequences for the UK economy of the past month’s policy experiment?
• What are the international implications?

As with all members events, questions from the audience drive the conversation. 

This event is in partnership with Fathom Consulting.

What is Labour’s foreign policy? 24 January 2023 — 12:00PM TO 1:00PM Anonymous (not verified) 3 January 2023 Chatham House and Online

In conversation with David Lammy, the UK shadow foreign secretary.

David Lammy MP, shadow secretary of state for foreign, commonwealth and development affairs, outlines Labour’s plan for UK foreign policy if elected to government.

He addresses the UK’s strengths and opportunities in a world that has become more divided, more dangerous, and more unpredictable. He also offers a critique of the current UK government’s approach to foreign policy, particularly at strained relationships with allies and Britain’s economic woes.

The shadow foreign secretary explores the following key questions:

• What would a future Labour government do to modernize Britain’s diplomacy and rebuild alliances to improve Britain’s global influence?

• In a new age of warfare in Europe, how would Labour pursue security cooperation with allies?

• How would Labour address high energy costs, energy security, and the climate crisis?

• As Britain’s economy falters, how can foreign policy drive prosperity at home?

• What is Labour’s plan for international development, following the UK government’s abandonment of the 0.7% commitment?

As with all members events, questions from the audience drive the conversation.

Read a transcript

Chatham House Primer: Social media and democracy 21 March 2023 — 6:00PM TO 6:45PM Anonymous (not verified) 23 February 2023 Chatham House

From the Arab Spring to the 2016 Trump election win, how have democracies benefited and suffered from the impact of social media? 

With social media now a well-entrenched, yet still recent, component of societies, democracies are still grappling with the impact bought about by this new form of communication and promotion.

For all that social media has bought people closer together and brought government, business and civic leaders, it has also been said to have fuelled divisions and hate. Governments and businesses are now drawing battle lines on the legal responsibilities required of social media platforms as we slowly determine the role they play in our society.

This Primer will discuss key questions including:

• What are the current legal responsibilities of social media companies? What sort of laws and regulations must they abide by?
• How are governments looking to change to this?
• How have some countries manipulated social media to monitor and censor their populations?
• Can social media truly tackle harmful and dangerous content?
• Is it possible to combat disinformation and what role should social media platforms play?
• How can we make social media best fit our society in the future?
• How should we govern online space?

A drinks reception will follow this event.

As with all member events, questions from the audience drive the conversation.

From Iraq to Ukraine: What did governments learn? 20 March 2023 — 12:00PM TO 1:00PM Anonymous (not verified) 6 March 2023 Chatham House and Online

What were the main lessons for today’s conflicts from the way in which the war in Iraq played out?

This March marks the 20th anniversary of the US and UK-led invasion of Iraq to oust Saddam Hussein. Based primarily on unfounded fears Iraq’s WMD (weapons of mass destruction) capability was buidling up in the absence of UN inspection and constraints on the IAEA (International Atomic Energy Agency) safeguards, the decision to go to war has reverberated throughout the Middle East, the intelligence communities, and Western political decision-making ever since.

In the 2002–03 period when UN inspectors were allowed back into Iraq, Hans Blix, chairman of UNMOVIC (UN Monitoring, Verification and Inspection Commission) and Mohamed ElBaradei, director general of the IAEA, were at the centre of a storm in which they were put under huge pressure to agree with the US/UK narrative on the ‘missing’ WMD.

Their problem was that the evidence they were uncovering did not support the claims, but the war went ahead – and Saddam was overthrown – despite these UN findings.

Much has changed since 2003. As the geopolitical landscape has shifted, so have geopolitics and capabilities. Today’s Russia’s war against Ukraine which includes WMD threats, cyberattacks, and an assertive disinformation campaign has opened up new ways of thinking about communicating information from open source and government intelligence analysis.

This panel explores the experiences of people involved with decision-making at the UN and in the UK in 2003 and how things have changed today.

• What were the lessons from the way in which the war in Iraq played out?
• How has that influenced the way in which NATO has responded to Russia’s wars against Ukraine?
• How should information be communicated within governments and to the public?
• How to deal with disinformation campaigns in the days of open source information and social media?

As with all member events, questions from the audience drive the conversation.

Chatham House exhibition - In conversation with the future 19 April 2023 — 6:00PM TO 8:00PM Anonymous (not verified) 31 March 2023 Chatham House

Hear from the innovative leaders and companies driving change towards a more sustainable future.

This event is an opportunity to hear from the innovative leaders and companies driving change towards a more sustainable future.

The evening begins with a panel discussion then, over sustainably sourced drinks and canapés, you are invited to walk through Chatham House and explore the innovative and experimental ideas enabling radical shifts to allow us to prosper without exhausting our planet’s resources.

Our exhibiting partners include Earthshot Prize winner NotPla, Hawkins Brown, Polymateria, and BEEN London. 

Bronwen Maddox, director of Chatham House, opens the evening at 6pm and introduces our panel of experts, chaired by Ana Yang, head of Chatham House’s Sustainability Accelerator. 

Please note that this event is operating a ballot for in-person attendance. Your place will be confirmed by Wednesday 12 April if you are successful.

This analysis aimed to identify clinical factors associated with positivity on repeat ⁶⁸Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 ⁶⁸Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann–Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2–1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9–3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative ⁶⁸Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat ⁶⁸Ga-PSMA-11 PET/CT.

Turkey in 2020 and Beyond: What Lies Ahead for Turkish Politics? 25 November 2019 — 12:30PM TO 1:30PM Anonymous (not verified) 6 November 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE

Turkey witnessed some major developments over the last year. In August 2018, the dramatic Lira devaluation caused the Turkish economy to go into recession. In the 2019 local elections, which took place during the economic downturn, the Republican Peoples’ Party (CHP) mayoral candidates took control of Ankara and Istanbul after 25 years of dominance by the ruling Justice and Development Party (AKP).

The election results might lead to a rethink of the AKP leadership and consequences on Turkish politics will depend on Erdoğan’s interpretation of this reversal of his political fortune.

Will this affect the long-standing alliance between AKP and MHP that has characterised Turkish foreign policy for the past few years? What impact will this have on both the domestic and international level? Finally, will Turkey’s recent incursion into Syria have lasting effect on the country’s alliances with other powers and its standing?

In this context, the speaker will analyse the significance of these changes and the future trajectory of Turkish politics, economics and foreign policy.

Mattel has apologized after inadvertently directing customers of its new line of Wicked dolls to a pornographic website, stating it is taking action to remove the misprinted toys' packaging.

Mattel has apologized after inadvertently directing customers of its new line of Wicked dolls to a pornographic website, stating it is taking action to remove the misprinted toys' packaging.

HPC news headlines often highlight the latest hardware speeds and feeds. While advances on the hardware front are important, improving the ability to write software for advanced systems is equally […]

The post What’s New with Chapel? Nine Questions for the Development Team appeared first on HPCwire.

New cross-species research suggests a theory of mind is one thing that sets humans apart from apes

The wealthiest person on Earth has taken the next step toward a commercial brain interface

From meditation to smiling, researchers take a second look at studies claiming to reveal what makes us happy

This banner year for elections worldwide may witness the arrival of advertising tailored to your personality

A grassroots online movement has helped shift the way scientists think about asexuality. But much is still unknown.

Red Hat has announced a signed agreement to acquire Neural Magic, a developer of software and algorithms that accelerate generative AI (gen AI) inference workloads. Red Hat mentions Neural Magic’s […]

The post Red Hat Acquisition Charts Path to Open Accelerated AI appeared first on HPCwire.

Actor Anne Hathaway turns 42 and actor Raffey Cassidy turns 23, among the famous birthdays for Nov. 12.

When negative feelings accumulate in a relationship, it can become a problem.

Your brain could stay sharp for years just by doing these simple activities.

Study of women over 50 suggests how to cut dementia risk by 90 percent.

Around 3% of people are thought to hear voices when there is no one talking.

Discover the hidden force shaping your social habits—and why you’re not even aware of it.

Learn how your darkest emotions can actually be your strongest motivators.