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Interleukin-12 electroporation may sensitize 'cold' melanomas to immunotherapies

(American Association for Cancer Research) Combining intratumoral electroporation of interleukin-12 (IL-12) DNA (tavokinogene telseplasmid, or TAVO) with the immune checkpoint inhibitor pembrolizumab (Keytruda) led to clinical responses in patients with immunologically quiescent advanced melanoma, according to results from a phase II trial.




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Deformed skulls in an ancient cemetery reveal a multicultural community in transition

(PLOS) The ancient cemetery of Mözs-Icsei d?l? in present-day Hungary holds clues to a unique community formation during the beginnings of Europe's Migration Period, according to a study published April 29, 2020 in the open-access journal PLOS ONE by Corina Knipper from the Curt-Engelhorn-Center for Archaeometry, Germany, István Koncz, Tivadar Vida from the Eötvös Loránd University, Budapest, Hungary and colleagues.




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The Maestro Project: A Patient Navigator for the Transition of Care for Youth With Type 1 Diabetes

Norma Van Walleghem
Feb 1, 2011; 24:9-13
From Research to Practice/Transitions in Young Adults with Type 1 Diabetes




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Transitions in Care from the Hospital to Home for Patients With Diabetes

Karen B. Hirschman
Aug 1, 2014; 27:192-195
From Research to Practice




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Breaking the Cycle of Violence: Transitional Justice for the Victims of ISIS in Syria

28 April 2020

This paper aims to assist the region’s local authorities, and their key foreign backers, in understanding how transitional justice can provide alternative avenues for holding local ISIS members to account while contributing to the healing of communities.

Haid Haid

Senior Consulting Fellow, Middle East and North Africa Programme

2020-04-28-Syria-prison.jpg

A fighter with the Syrian Democratic Forces monitors prisoners accused of being affiliated with ISIS, at a prison in the northeastern Syrian city of Hassakeh on 25 October 2019. Photo: Getty Images.

Summary

  • Following the territorial defeat of Islamic State of Iraq and Syria (ISIS) in northeastern Syria, the Kurdish-led autonomous administration in the region is now grappling with the task of quickly dealing with thousands of the group’s detained members while bringing justice to their victims. To that end, local authorities are focusing on the use of counterterrorism laws and courts to charge captured ISIS members and determine their guilt accordingly.
  • The piecemeal approach to justice is deeply flawed, and raises particular concerns about due process. No precise instruments exist to determine the personal responsibility of ISIS individuals for specific crimes, or for their role in war crimes committed by the group. In any event, the scale of the crimes and the number of victims – as well as severe shortages of resources and workers – make dispensation of justice extremely difficult through the traditional legal system.
  • Not all detained ISIS members receive prison sentences. Individuals who did not hold senior roles in the group’s apparatus and are not accused of ‘major’ crimes (in practice, largely defined as fighting for ISIS and murder) are being released under limited reconciliation deals with tribal leaders. But the involvement of local community leaders in those efforts is not enough to ensure positive results. Many victims are upset at seeing ISIS members walk free without even admitting their guilt publicly or apologizing for the pain they caused.
  • To overcome the limitations of the current, counterterrorism-focused framework, a ‘transitional justice’ approach could provide judicial and non-judicial instruments to establish accountability for ISIS crimes and reduce community resistance to the reintegration of group members. A combination of non-judicial mechanisms such as truth commissions, missing persons’ committees, and reparations and victim-healing programmes could play a vital role in providing ISIS victims with a sense of justice while contributing to peacebuilding and stability.
  • Ignoring the urgency of developing a long-term plan to serve justice and contribute to community healing will almost certainly allow ISIS to continue to prevent the recovery and development of northeastern Syria. This, in turn, risks undermining the stability of the country and the region at large.




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Webinar: Breaking the Cycle of Violence: Transitional Justice for the Victims of ISIS in Syria

Research Event

12 May 2020 - 2:00pm to 3:00pm
Add to Calendar

Haid Haid, Senior Consulting Fellow, Middle East and North Africa Programme, Chatham House
Sara Kayyali, Syria Researcher, Middle East and North Africa Division, Human Rights Watch
Moderator: Lina Khatib, Director, Middle East and North Africa Programme, Chatham House

You can register your interest here. Alternatively, you can watch the webinar live on the MENA Programme Facebook page.

Following the territorial defeat of Islamic State of Iraq and Syria (ISIS) in northeastern Syria, the Kurdish-led autonomous administration in the region is now grappling with the task of quickly dealing with thousands of the group’s detained members while bringing justice to their victims. To that end, local authorities are focusing on the use of counterterrorism laws and courts to charge captured ISIS members and determine their guilt accordingly.

In a recent research paper, author Haid Haid argues that this approach to justice is deeply flawed as it raises concerns about due process and lacks the precise instruments to determine the personal responsibility of ISIS individuals for specific crimes, or for their role in war crimes committed by the group. The paper proposes that a ‘transitional justice’ approach could provide judicial and non-judicial instruments to establish accountability for ISIS crimes and reduce community resistance to the reintegration of group members.

In this webinar, part of the MENA Programme’s Online Event Series, speakers will examine the benefits of such an approach to justice for overcoming the limitations of the current, counterterrorism-focused framework. Panelists will discuss the alternative mechanisms local authorities and their key foreign backers can use to hold local ISIS members to account while contributing to the healing of communities.
 
The event will be held on the record.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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MaXLinker: Proteome-wide Cross-link Identifications with High Specificity and Sensitivity [Technological Innovation and Resources]

Protein-protein interactions play a vital role in nearly all cellular functions. Hence, understanding their interaction patterns and three-dimensional structural conformations can provide crucial insights about various biological processes and underlying molecular mechanisms for many disease phenotypes. Cross-linking mass spectrometry (XL-MS) has the unique capability to detect protein-protein interactions at a large scale along with spatial constraints between interaction partners. The inception of MS-cleavable cross-linkers enabled the MS2-MS3 XL-MS acquisition strategy that provides cross-link information from both MS2 and MS3 level. However, the current cross-link search algorithm available for MS2-MS3 strategy follows a "MS2-centric" approach and suffers from a high rate of mis-identified cross-links. We demonstrate the problem using two new quality assessment metrics ["fraction of mis-identifications" (FMI) and "fraction of interprotein cross-links from known interactions" (FKI)]. We then address this problem, by designing a novel "MS3-centric" approach for cross-link identification and implementing it as a search engine named MaXLinker. MaXLinker outperforms the currently popular search engine with a lower mis-identification rate, and higher sensitivity and specificity. Moreover, we performed human proteome-wide cross-linking mass spectrometry using K562 cells. Employing MaXLinker, we identified a comprehensive set of 9319 unique cross-links at 1% false discovery rate, comprising 8051 intraprotein and 1268 interprotein cross-links. Finally, we experimentally validated the quality of a large number of novel interactions identified in our study, providing a conclusive evidence for MaXLinker's robust performance.




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Glucose availability but not changes in pancreatic hormones sensitizes hepatic AMPK activity during nutritional transition in rodents [Metabolism]

The cellular energy sensor AMP-activated protein kinase (AMPK) is a metabolic regulator that mediates adaptation to nutritional variations to maintain a proper energy balance in cells. We show here that suckling-weaning and fasting-refeeding transitions in rodents are associated with changes in AMPK activation and the cellular energy state in the liver. These nutritional transitions were characterized by a metabolic switch from lipid to glucose utilization, orchestrated by modifications in glucose levels and the glucagon/insulin ratio in the bloodstream. We therefore investigated the respective roles of glucose and pancreatic hormones on AMPK activation in mouse primary hepatocytes. We found that glucose starvation transiently activates AMPK, whereas changes in glucagon and insulin levels had no impact on AMPK. Challenge of hepatocytes with metformin-induced metabolic stress strengthened both AMPK activation and cellular energy depletion under limited-glucose conditions, whereas neither glucagon nor insulin altered AMPK activation. Although both insulin and glucagon induced AMPKα phosphorylation at its Ser485/491 residue, they did not affect its activity. Finally, the decrease in cellular ATP levels in response to an energy stress was additionally exacerbated under fasting conditions and by AMPK deficiency in hepatocytes, revealing metabolic inflexibility and emphasizing the importance of AMPK for maintaining hepatic energy charge. Our results suggest that nutritional changes (i.e. glucose availability), rather than the related hormonal changes (i.e. the glucagon/insulin ratio), sensitize AMPK activation to the energetic stress induced by the dietary transition during fasting. This effect is critical for preserving the cellular energy state in the liver.




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Inhibition of the polyamine synthesis enzyme ornithine decarboxylase sensitizes triple-negative breast cancer cells to cytotoxic chemotherapy [Molecular Bases of Disease]

Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.




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China's 2020: Economic Transition, Sustainability and the Coronavirus

Corporate Members Event

10 March 2020 - 12:15pm to 2:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham House
David Lubin, Associate Fellow, Global Economy and Finance Programme, Chatham House; Managing Director and Head of Emerging Markets Economics, Citi
Jinny Yan, Managing Director and Chief China Economist, ICBC Standard
Chair: Creon Butler, Director, Global Economy and Finance Programme, Chatham House

Read all our analysis on the Coronavirus Response

The coronavirus outbreak comes at a difficult time for China’s ruling party. A tumultuous 2019 saw the country fighting an economic slowdown coupled with an increasingly hostile international environment. As authorities take assertive steps to contain the virus, the emergency has - at least temporarily - disrupted global trade and supply chains, depressed asset prices and forced multinational businesses to make consequential decisions with limited information. 

Against this backdrop, panellists reflect on the country’s nascent economic transition from 2020 onward. What has been China’s progress towards a sustainable innovation-led economy so far? To what extent is the ruling party addressing growing concerns over job losses, wealth inequality and a lack of social mobility? And how are foreign investors responding to these developments in China?

Members Events Team




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Development of a sensitive and quantitative method for the identification of two major furan fatty acids in human plasma

Long Xu
Apr 1, 2020; 61:560-569
Methods




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Promoting a Just Transition to an Inclusive Circular Economy

1 April 2020

Considerations of justice and social equity are as important for the circular economy transition as they are in the contexts of low-carbon transitions and digitalization of the economy. This paper sets out the just transition approach, and its relevance in climate change and energy transition debates.

Patrick Schröder

Senior Research Fellow, Energy, Environment and Resources Programme

2020-04-01-circular-economy.jpg

Residents of Mount Ijen take sulphur at Ijen Crater, Banyuwangi, East Java, on 2 July 2018. Photo: Getty Images.

Summary

  • Many social and political issues have so far been neglected in planning for the circular economy transition. This paper aims to redress this by considering how ‘just transition’ and social equity may be achieved through policy and practice.
  • The prevailing economic model is linear, in that resources are extracted, transformed into products, used, and finally discarded. In contrast, the circular economy recognizes that natural resources are finite, and aims to keep the materials in products in circulation for as long as possible: reusing, repairing, remanufacturing, sharing and recycling. While the concept of the circular economy is largely focused on developing new technologies and businesses to enable keeping materials in circulation, it also includes the notions of ‘designing out’ waste, substituting renewable materials for non-renewable ones, and restoring natural systems.
  • The UN 2030 Agenda demonstrates that environmental, social and economic sustainability objectives cannot be separated. As the links between the environmental issues of climate change, overconsumption of resources and waste generation, and social issues of inequality and the future of work become increasingly obvious, the urgency to connect environmental with social justice is gaining in significance. The language of ‘just transition’ – a transition that ensures environmental sustainability, decent work, social inclusion and poverty eradication – has started to penetrate debates and research on sustainability policy, particularly in the contexts of climate change and low-carbon energy transition.
  • A just transition framework for the circular economy can identify opportunities that reduce waste and stimulate product innovation, while at the same time contributing positively to sustainable human development. And a just transition is needed to reduce inequalities within and between countries, and to ensure that the commitment of the UN Sustainable Development Goals to leave no one behind is fulfilled.
  • It is important to identify the likely impacts on employment as a result of digitalization and industrial restructuring. Combining circular economy policies with social protection measures will be important in order to ensure that the burden of efforts to promote circularity will not fall on the poor through worsening working conditions and health impacts, reduced livelihoods, or job losses. Identifying potential winners and losers through participatory ‘roadmapping’ can help shape effective cooperation mechanisms and partnerships nationally and internationally.
  • Many low- and middle-income countries that rely heavily on ‘linear’ sectors such as mining, manufacturing of non-repairable fast-moving consumer goods, textiles and agriculture, and the export of these commodities to higher-income countries, are likely to be negatively affected by the shift to circularity. These countries will need support from the international community through targeted assistance programmes if international trade in established commodities and manufactures declines in the medium to long term. 
  • International cooperation to create effective and fair governance mechanisms, and policy coordination at regional, national and local levels will play an important role in shaping a just transition. Multilateral technical assistance programmes will need to be designed and implemented, in particular to support low- and middle-income countries.
  • Governments, international development finance institutions and banks are among the bodies beginning to establish circular economy investment funds and programmes. Just transition principles are yet to be applied to many of these new finance mechanisms, and will need to be integrated into development finance to support the circular economy transition.
  • New international cooperation programmes, and a global mechanism to mobilize dedicated support funds for countries in need, will be critical to successful implementation across global value chains. Transparent and accountable institutions will also be important in ensuring that just transition funds reach those affected as intended.




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Economic Crisis and the Delayed Arrival of a New President: Transition Trauma

1 November 2008 , Number 1

The new American president will not be inaugurated until January 20. He will certainly face the most difficult economic conditions since Franklin Roosevelt entered the White House in March 1933. The politics of presidential transition – in this year, as seventy-six years ago – seem likely only to exacerbate the global crisis.

John Dumbrell

Professor of Government, Durham University




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Breaking the Cycle of Violence: Transitional Justice for the Victims of ISIS in Syria

28 April 2020

This paper aims to assist the region’s local authorities, and their key foreign backers, in understanding how transitional justice can provide alternative avenues for holding local ISIS members to account while contributing to the healing of communities.

Haid Haid

Senior Consulting Fellow, Middle East and North Africa Programme

2020-04-28-Syria-prison.jpg

A fighter with the Syrian Democratic Forces monitors prisoners accused of being affiliated with ISIS, at a prison in the northeastern Syrian city of Hassakeh on 25 October 2019. Photo: Getty Images.

Summary

  • Following the territorial defeat of Islamic State of Iraq and Syria (ISIS) in northeastern Syria, the Kurdish-led autonomous administration in the region is now grappling with the task of quickly dealing with thousands of the group’s detained members while bringing justice to their victims. To that end, local authorities are focusing on the use of counterterrorism laws and courts to charge captured ISIS members and determine their guilt accordingly.
  • The piecemeal approach to justice is deeply flawed, and raises particular concerns about due process. No precise instruments exist to determine the personal responsibility of ISIS individuals for specific crimes, or for their role in war crimes committed by the group. In any event, the scale of the crimes and the number of victims – as well as severe shortages of resources and workers – make dispensation of justice extremely difficult through the traditional legal system.
  • Not all detained ISIS members receive prison sentences. Individuals who did not hold senior roles in the group’s apparatus and are not accused of ‘major’ crimes (in practice, largely defined as fighting for ISIS and murder) are being released under limited reconciliation deals with tribal leaders. But the involvement of local community leaders in those efforts is not enough to ensure positive results. Many victims are upset at seeing ISIS members walk free without even admitting their guilt publicly or apologizing for the pain they caused.
  • To overcome the limitations of the current, counterterrorism-focused framework, a ‘transitional justice’ approach could provide judicial and non-judicial instruments to establish accountability for ISIS crimes and reduce community resistance to the reintegration of group members. A combination of non-judicial mechanisms such as truth commissions, missing persons’ committees, and reparations and victim-healing programmes could play a vital role in providing ISIS victims with a sense of justice while contributing to peacebuilding and stability.
  • Ignoring the urgency of developing a long-term plan to serve justice and contribute to community healing will almost certainly allow ISIS to continue to prevent the recovery and development of northeastern Syria. This, in turn, risks undermining the stability of the country and the region at large.




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Kazakhstan: Tested by Transition

Invitation Only Research Event

28 November 2019 - 1:30pm to 3:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Annette Bohr, Associate Fellow, Russia and Eurasia Programme, Chatham House
Kassymkhan Kapparov, Founder, Economist.kz
Joanna Lillis, Reporter, The Guardian, The Economist and The Independent
Kate Mallinson, Associate Fellow, Russia and Eurasia Programme, Chatham House
Dossym Satpayev, Director, Kazakhstan Risk Assessment Group; Member of the Presidium, Kazakhstan Council on International Relations
Chair: James Nixey, Head, Russia and Eurasia Programme, Chatham House

At face value at least, Central Asia’s wealthiest state has embarked on a bold experiment following the March 2019 decision by its founding father and long-standing ruler, Nursultan Nazarbayev, to resign from the presidency and initiate a managed political succession. A generational transition of this nature, untried in other former Soviet republics, brings with it high stakes.
 
As well as seeking to secure his own legacy, having dominated the country since before independence in 1991, Nazarbayev wants to ensure Kazakhstan does not depart from the course he has set while safeguarding Kazakhstan’s stability in the context of multiple and evolving domestic and international challenges. But this is easier said than done. Is Kazakhstan ready for the challenges of the future?
 
This event marks the launch of Chatham House’s major report Kazakhstan: Tested by Transition.

Department/project

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Kazakhstan: Tested by Transition

27 November 2019

A partial handover of political power through an orchestrated transition takes Kazakhstan into uncharted territory. Will it be able to pursue modernization and reform, and break from its authoritarian past?

Annette Bohr

Associate Fellow, Russia and Eurasia Programme

Dr Nigel Gould-Davies

Associate Fellow, Russia and Eurasia Programme, Chatham House

Kate Mallinson

Associate Fellow, Russia and Eurasia Programme

James Nixey

Director, Russia and Eurasia Programme

Birgit Brauer

Analyst, Writer and Journalist Covering Central Asia

Nargis Kassenova

Senior Fellow, Davis Center for Russian and Eurasian Studies, Harvard University

Joanna Lillis

Kazakhstan-Based Journalist Reporting on Central Asia

Dosym Satpayev

Independent Political Analyst and the Director of the Kazakhstan Risks Assessment Group

Kazakhstan is at a turning point in its history. At face value, at least, Central Asia’s wealthiest state has embarked on a bold experiment following the March 2019 decision by its founding father and long-standing ruler, Nursultan Nazarbayev, to resign from the presidency and initiate a managed political succession. A generational transition of this nature, untried in other former Soviet republics, brings with it high stakes. As well as looking to secure his own legacy, having dominated the country since before independence in 1991, Nazarbayev seeks to ensure Kazakhstan does not depart from the course he has set, while safeguarding regime stability in the context of multiple and evolving domestic and international challenges. This is easier said than done.

The uncertainty around this project is substantial, especially considering a ‘rowback’ decree just seven months after Nazarbayev’s resignation, limiting the powers of his anointed successor, Kassym-Jomart Tokayev. How long can Tokayev credibly remain president considering such a transparent undermining of his authority? Is Nazarbayev, in fact, grooming his daughter, Dariga Nazarbayeva, another relative or a power player from outside the family for the leadership in the longer term? Will the ‘Kazakh tandem’ of Nazarbayev and Tokayev function effectively, or will tensions and conflicts arise between them as many claim is happening already? How will the leadership cope with the protest mood now manifest on the streets of Kazakhstan, and address the political and socio-economic grievances fuelling this discontent? How might the political transition play out if Nazarbayev were to suddenly exit the political scene altogether?And what is the long-term transition plan for the time when Nazarbayev has departed, and how effective will it be?

As Kazakhstan enters uncharted territory, the purpose of this report is twofold. First, to make the case for the West to devote more attention to Kazakhstan. The country’s relative importance in Central Asia, and as the constant focus of intense attention from China and Russia, suggests that the West is wrong to direct so little time and diplomatic effort and so few resources towards it. This is not so much a miscalculation (that would be to assume there had been a calculation in the first place) as a misstep through neglect, presupposing that the future will resemble the present – with Kazakhstan remaining stable internally, relatively inconsequential geopolitically but nevertheless a friendly ally to the West. In fact, the country’s trajectory over the next few years is of potentially strategic import. This is because even its political semi-transition presents the West with a rare opportunity to push back against the global rise of authoritarianism, in a state that is open to rational argument and economic logic.

The second function of the report is to serve as a well-intentioned message to the leadership of Kazakhstan. The research undertaken by the report’s eight authors shows that Kazakhstan is at risk of failing to achieve the goals its leadership has set for the country. As significant as it has been, the partial stepping aside of Nazarbayev by no means guarantees the modernization and renewal that he and his successor have promised. Far deeper political, economic and social reforms will be needed if Kazakhstan is to meet the growing challenges to its stability, prosperity and development. Street protests since Nazarbayev’s resignation have demonstrated a level of popular disaffection far higher than the authorities acknowledge. The leadership needs to bridge the disconnect between the rulers and the ruled and start listening to its people.

To avoid slipping into decline, and to resist external pressures and geopolitical overtures that could diminish the sovereignty that its leadership is so determined to safeguard, Kazakhstan needs new faces – innovators and reformers – throughout every level of the administration, as well as new ideas. This report is intended to help with the ‘ideas’ part of that proposition. It also includes a series of recommendations for Western governments and institutions and for the Kazakhstan government. 




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POSTPONED: Transitional Justice in Ukraine: What Might it Look Like?

Invitation Only Research Event

17 March 2020 - 9:30am to 1:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Kirsty Brimelow QC, Barrister, Doughty Street Chambers
Miles Jackson, Associate Professor of Law, University of Oxford
Anton Korynevych, Representative of the President of Ukraine for Crimea
Oleksandra Matviychuk, Head of the Board, Centre for Civil Liberties
Taras Tsymbrivksyy, Head, USAID Human Rights in Action Program; Ukrainian Helsinki Human Rights Union

Still grappling with the war in the east and the occupation of Crimea, Ukraine’s new leadership has announced its intention to develop its transitional justice infrastructure to respond to the human rights violations arising from Russia’s aggression. 

Numerous reports (not least ones by the UN Human Rights Monitoring Mission in Ukraine) list persecutions, illegal detentions, enforced disappearances, torture and killings among the crimes perpetrated in Crimea and parts of occupied Donbas. 

As Ukraine has only just started developing its transitional justice roadmap, this event will seek to discuss viable initial approaches, such as a ‘truth-telling commission’ or amnesties. 

The panellists will also discuss the role for civil society and those directly affected by hostilities in the transitional justice process.  

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Event attributes

Chatham House Rule

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Endocytosis of very low-density lipoproteins: an unexpected mechanism for lipid acquisition by breast cancer cells [Research Articles]

We previously described the expression of CD36 and LPL by breast cancer (BC) cells and tissues and the growth-promoting effect of VLDL observed only in the presence of LPL. We now report a model in which LPL is bound to a heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the VLDL receptor to internalize VLDLs via receptor-mediated endocytosis. We also demonstrate that gene-expression programs for lipid synthesis versus uptake respond robustly to triglyceride-rich lipoprotein availability. The literature emphasizes de novo FA synthesis and exogenous free FA uptake using CD36 as paramount mechanisms for lipid acquisition by cancer cells. We find that the uptake of intact lipoproteins is also an important mechanism for lipid acquisition and that the relative reliance on lipid synthesis versus uptake varies among BC cell lines and in response to VLDL availability. This metabolic plasticity has important implications for the development of therapies aimed at the lipid dependence of many types of cancer, in that the inhibition of FA synthesis may elicit compensatory upregulation of lipid uptake. Moreover, the mechanism that we have elucidated provides a direct connection between dietary fat and tumor biology.­.




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High density lipoprotein and its apolipoprotein-defined subspecies and risk of dementia [Patient-Oriented and Epidemiological Research]

Whether HDL is associated with dementia risk is unclear. In addition to apoA1, other apolipoproteins are found in HDL, creating subspecies of HDL that may have distinct metabolic properties. We measured apoA1, apoC3, and apoJ levels in plasma and apoA1 levels in HDL that contains or lacks apoE, apoJ, or apoC3 using a modified sandwich ELISA in a case-cohort study nested within the Ginkgo Evaluation of Memory Study. We included 995 randomly selected participants and 521 participants who developed dementia during a mean of 5.1 years of follow-up. The level of total apoA1 was not significantly related to dementia risk, regardless of the coexistence of apoC3, apoJ, or apoE. Higher levels of total plasma apoC3 were associated with better cognitive function at baseline (difference in Modified Mini-Mental State Examination scores tertile 3 vs. tertile 1: 0.60; 95% CI: 0.23, 0.98) and a lower dementia risk (adjusted hazard ratio tertile 3 vs. tertile 1: 0.73; 95% CI: 0.55, 0.96). Plasma concentrations of apoA1 in HDL and its apolipoprotein-defined subspecies were not associated with cognitive function at baseline or with the risk of dementia during follow-up. Similar studies in other populations are required to better understand the association between apoC3 and Alzheimer’s disease pathology.




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Development of a sensitive and quantitative method for the identification of two major furan fatty acids in human plasma [Methods]

This article focuses on the establishment of an accurate and sensitive quantitation method for the analysis of furan fatty acids. In particular, the sensitivity of GC/MS and UPLC/ESI/MS/MS was compared for the identification and quantification of furan fatty acids. Different methylation methods were tested with respect to GC/MS analysis. Special attention needs to be paid to the methylation of furan fatty acids, as acidic catalysts might lead to the degradation of the furan ring. GC/MS analysis in full-scan mode demonstrated that the limit of quantitation was 10 μM. UPLC/ESI/MS/MS in multiple reaction monitoring mode displayed a higher detection sensitivity than GC/MS. Moreover, the identification of furan fatty acids with charge-reversal derivatization was tested in the positive mode with two widely used pyridinium salts. Significant oxidation was unexpectedly observed using N-(4-aminomethylphenyl) pyridinium as a derivatization agent. The formed 3-acyl-oxymethyl-1-methylpyridinium iodide derivatized by 2-bromo-1-methylpyridinium iodide and 3-carbinol-1-methylpyridinium iodide improved the sensitivity more than 2,000-fold compared with nonderivatization in the negative mode by UPLC/ESI/MS/MS. This charge-reversal derivatization enabled the targeted quantitation of furan fatty acids in human plasma. Thus, it is anticipated that this protocol could greatly contribute to the clarification of pathological mechanisms related to furan fatty acids and their metabolites.




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Delineating an extracellular redox-sensitive module in T-type Ca2+ channels [Membrane Biology]

T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.




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Pathogenic Role of PPAR{alpha} Down-Regulation in Corneal Nerve Degeneration and Impaired Corneal Sensitivity in Diabetes

The purpose of this study was to investigate the protective role of Peroxisome Proliferator-Activated Receptor-alpha (PPARα) against diabetic keratopathy and corneal neuropathy. Corneal samples were obtained from diabetic and non-diabetic human donors. Streptozotocin-induced diabetic rats and mice were orally treated with PPARα agonist fenofibrate. As shown by immunohistochemistry and Western blotting, PPARα was down-regulated in the corneas of diabetic humans and rats. Immunostaining of β-III tubulin demonstrated that corneal nerve fiber metrics were decreased significantly in diabetic rats and mice, which was partially prevented by fenofibrate treatment. As evaluated using a Cochet-Bonnet aesthesiometer, corneal sensitivity was significantly decreased in diabetic mice, which was prevented by fenofibrate. PPARα-/- mice displayed progressive decreases in the corneal nerve fiber density. Consistently, corneal sensitivity was decreased in PPARα-/- mice relative to wild-type mice by nine months of age. Diabetic mice showed increased incidence of spontaneous corneal epithelial lesion, which was prevented by fenofibrate while exacerbated by PPARα knockout. Western blot analysis revealed significantly altered neurotrophic factor levels in diabetic rat corneas, which were partially restored by fenofibrate treatment. These results indicate that PPARα protects corneal nerve from degeneration induced by diabetes, and PPARα agonists have therapeutic potential in the treatment of diabetic keratopathy.




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Necrostatin-1 Mitigates Cognitive Dysfunction in Prediabetic Rats With no Alteration in Insulin Sensitivity

Previous studies show that 12-week of high-fat diet (HFD) consumption caused not only prediabetes, but also cognitive decline and brain pathologies. Recently, necrostatin-1 (nec-1), a necroptosis inhibitor, showed beneficial effects in brain against stroke. However, the comparative effects of nec-1 and metformin on cognition and brain pathologies in prediabetes have not been investigated. We hypothesized that nec-1 and metformin equally attenuated cognitive decline and brain pathologies in prediabetic rats. Rats (n=32) were fed with either normal diet (ND) or high-fat diet (HFD) for 20 weeks. At week 13, ND-fed rats were given a vehicle (n=8) and HFD-fed rats were randomly assigned into 3 subgroups (n=8/subgroup) with vehicle, nec-1 or metformin for 8 weeks. Metabolic parameters, cognitive function, brain insulin receptor function, synaptic plasticity, dendritic spine density, microglial morphology, brain mitochondrial function, Alzheimer’s protein, and cell death were determined. HFD-fed rats exhibited prediabetes, cognitive decline, and brain pathologies. Nec-1 and metformin equally improved cognitive function, synaptic plasticity, dendritic spine density, microglial morphology, brain mitochondrial function, reduced hyperphosphorylated-tau and necroptosis in HFD-fed rats. Interestingly metformin, but not nec-1, improved brain insulin sensitivity in those rats. In conclusion, necroptosis inhibition directly improved cognition in prediabetic rats without alteration in insulin sensitivity.




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Longitudinal Analysis of Serum Cytokine Levels and Gut Microbial Abundance Links IL-17/IL-22 with Clostridia and Insulin Sensitivity in Humans

Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22 producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis that early in the onset of metabolic diseases there is a decline in serum levels of IL-17/IL-22, with concomitant changes in the gut microbiome. Clustering iHMP study participants on the basis of longitudinal IL-17/IL-22 profiles identified discrete groups. Individuals distinguished by low levels of IL-17/IL-22 were linked to established markers of metabolic disease, including insulin sensitivity. These individuals also displayed gut microbiome dysbiosis, characterized by decreased diversity, and IL-17/IL-22-related declines in the phylum Firmicutes, class Clostridia, and order Clostridiales. This ancillary analysis of the iHMP data therefore supports a link between the gut microbiome, IL-17/IL-22 and the onset of metabolic diseases. This raises the possibility for novel, microbiome-related therapeutic targets that may effectively alleviate metabolic diseases in humans as they do in animal models.




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A Polymorphism in the Glucocorticoid Receptor Gene, Which Decreases Sensitivity to Glucocorticoids In Vivo, Is Associated With Low Insulin and Cholesterol Levels

Elisabeth F.C. van Rossum
Oct 1, 2002; 51:3128-3134
Genetics




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Correction: Histone demethylase KDM6B promotes epithelial-mesenchymal transition. [Additions and Corrections]

VOLUME 287 (2012) PAGES 44508–44517In Fig. 1A, the wrong image for the control group was presented. The authors inadvertently cropped the control images in Fig. 1, A and E, from the same raw image. Fig. 1A has now been corrected and does not affect the results or conclusions of the work. The authors sincerely apologize for their mistake during figure preparation and for any inconvenience this may have caused readers.jbc;295/19/6781/F1F1F1Figure 1A.




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Kazakhstan: Tested by Transition

Invitation Only Research Event

28 November 2019 - 1:30pm to 3:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Annette Bohr, Associate Fellow, Russia and Eurasia Programme, Chatham House
Kassymkhan Kapparov, Founder, Economist.kz
Joanna Lillis, Reporter, The Guardian, The Economist and The Independent
Kate Mallinson, Associate Fellow, Russia and Eurasia Programme, Chatham House
Dossym Satpayev, Director, Kazakhstan Risk Assessment Group; Member of the Presidium, Kazakhstan Council on International Relations
Chair: James Nixey, Head, Russia and Eurasia Programme, Chatham House

At face value at least, Central Asia’s wealthiest state has embarked on a bold experiment following the March 2019 decision by its founding father and long-standing ruler, Nursultan Nazarbayev, to resign from the presidency and initiate a managed political succession. A generational transition of this nature, untried in other former Soviet republics, brings with it high stakes.
 
As well as seeking to secure his own legacy, having dominated the country since before independence in 1991, Nazarbayev wants to ensure Kazakhstan does not depart from the course he has set while safeguarding Kazakhstan’s stability in the context of multiple and evolving domestic and international challenges. But this is easier said than done. Is Kazakhstan ready for the challenges of the future?
 
This event marks the launch of Chatham House’s major report Kazakhstan: Tested by Transition.

Department/project

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Kazakhstan: Tested by Transition

27 November 2019

A partial handover of political power through an orchestrated transition takes Kazakhstan into uncharted territory. Will it be able to pursue modernization and reform, and break from its authoritarian past?

Annette Bohr

Associate Fellow, Russia and Eurasia Programme

Dr Nigel Gould-Davies

Associate Fellow, Russia and Eurasia Programme, Chatham House

Kate Mallinson

Associate Fellow, Russia and Eurasia Programme

James Nixey

Director, Russia and Eurasia Programme

Birgit Brauer

Analyst, Writer and Journalist Covering Central Asia

Nargis Kassenova

Senior Fellow, Davis Center for Russian and Eurasian Studies, Harvard University

Joanna Lillis

Kazakhstan-Based Journalist Reporting on Central Asia

Dosym Satpayev

Independent Political Analyst and the Director of the Kazakhstan Risks Assessment Group

Kazakhstan is at a turning point in its history. At face value, at least, Central Asia’s wealthiest state has embarked on a bold experiment following the March 2019 decision by its founding father and long-standing ruler, Nursultan Nazarbayev, to resign from the presidency and initiate a managed political succession. A generational transition of this nature, untried in other former Soviet republics, brings with it high stakes. As well as looking to secure his own legacy, having dominated the country since before independence in 1991, Nazarbayev seeks to ensure Kazakhstan does not depart from the course he has set, while safeguarding regime stability in the context of multiple and evolving domestic and international challenges. This is easier said than done.

The uncertainty around this project is substantial, especially considering a ‘rowback’ decree just seven months after Nazarbayev’s resignation, limiting the powers of his anointed successor, Kassym-Jomart Tokayev. How long can Tokayev credibly remain president considering such a transparent undermining of his authority? Is Nazarbayev, in fact, grooming his daughter, Dariga Nazarbayeva, another relative or a power player from outside the family for the leadership in the longer term? Will the ‘Kazakh tandem’ of Nazarbayev and Tokayev function effectively, or will tensions and conflicts arise between them as many claim is happening already? How will the leadership cope with the protest mood now manifest on the streets of Kazakhstan, and address the political and socio-economic grievances fuelling this discontent? How might the political transition play out if Nazarbayev were to suddenly exit the political scene altogether?And what is the long-term transition plan for the time when Nazarbayev has departed, and how effective will it be?

As Kazakhstan enters uncharted territory, the purpose of this report is twofold. First, to make the case for the West to devote more attention to Kazakhstan. The country’s relative importance in Central Asia, and as the constant focus of intense attention from China and Russia, suggests that the West is wrong to direct so little time and diplomatic effort and so few resources towards it. This is not so much a miscalculation (that would be to assume there had been a calculation in the first place) as a misstep through neglect, presupposing that the future will resemble the present – with Kazakhstan remaining stable internally, relatively inconsequential geopolitically but nevertheless a friendly ally to the West. In fact, the country’s trajectory over the next few years is of potentially strategic import. This is because even its political semi-transition presents the West with a rare opportunity to push back against the global rise of authoritarianism, in a state that is open to rational argument and economic logic.

The second function of the report is to serve as a well-intentioned message to the leadership of Kazakhstan. The research undertaken by the report’s eight authors shows that Kazakhstan is at risk of failing to achieve the goals its leadership has set for the country. As significant as it has been, the partial stepping aside of Nazarbayev by no means guarantees the modernization and renewal that he and his successor have promised. Far deeper political, economic and social reforms will be needed if Kazakhstan is to meet the growing challenges to its stability, prosperity and development. Street protests since Nazarbayev’s resignation have demonstrated a level of popular disaffection far higher than the authorities acknowledge. The leadership needs to bridge the disconnect between the rulers and the ruled and start listening to its people.

To avoid slipping into decline, and to resist external pressures and geopolitical overtures that could diminish the sovereignty that its leadership is so determined to safeguard, Kazakhstan needs new faces – innovators and reformers – throughout every level of the administration, as well as new ideas. This report is intended to help with the ‘ideas’ part of that proposition. It also includes a series of recommendations for Western governments and institutions and for the Kazakhstan government. 




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POSTPONED: Transitional Justice in Ukraine: What Might it Look Like?

Invitation Only Research Event

17 March 2020 - 9:30am to 1:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Kirsty Brimelow QC, Barrister, Doughty Street Chambers
Miles Jackson, Associate Professor of Law, University of Oxford
Anton Korynevych, Representative of the President of Ukraine for Crimea
Oleksandra Matviychuk, Head of the Board, Centre for Civil Liberties
Taras Tsymbrivksyy, Head, USAID Human Rights in Action Program; Ukrainian Helsinki Human Rights Union

Still grappling with the war in the east and the occupation of Crimea, Ukraine’s new leadership has announced its intention to develop its transitional justice infrastructure to respond to the human rights violations arising from Russia’s aggression. 

Numerous reports (not least ones by the UN Human Rights Monitoring Mission in Ukraine) list persecutions, illegal detentions, enforced disappearances, torture and killings among the crimes perpetrated in Crimea and parts of occupied Donbas. 

As Ukraine has only just started developing its transitional justice roadmap, this event will seek to discuss viable initial approaches, such as a ‘truth-telling commission’ or amnesties. 

The panellists will also discuss the role for civil society and those directly affected by hostilities in the transitional justice process.  

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Event attributes

Chatham House Rule

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Quantification of the Relationship Between Insulin Sensitivity and {beta}-Cell Function in Human Subjects: Evidence for a Hyperbolic Function

Steven E Kahn
Nov 1, 1993; 42:1663-1672
Original Article




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Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion

HE Hohmeier
Mar 1, 2000; 49:424-430
Articles




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Interplay of Placental DNA Methylation and Maternal Insulin Sensitivity in Pregnancy

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ~26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 x 10–8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1. Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.




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Marte confident transition to CF will be smooth

Ketel Marte does not lack for confidence when it comes to switching from second base/shortstop to center field, which is where he's expected to see a lot of time this season.




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PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes

Type 1 diabetes mellitus (T1DM) has traditionally been characterized by a complete destruction of β-cell mass (BCM); however, there is growing evidence of possible residual BCM present in T1DM. Given the absence of in vivo tools to measure BCM, routine clinical measures of β-cell function (e.g., C-peptide release) may not reflect BCM. We previously demonstrated the potential utility of PET imaging with the dopamine D2 and D3 receptor agonist 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (11C-(+)-PHNO) to differentiate between healthy control (HC) and T1DM individuals. Methods: Sixteen individuals participated (10 men, 6 women; 9 HCs, 7 T1DMs). The average duration of diabetes was 18 ± 6 y (range, 14–30 y). Individuals underwent PET/CT scanning with a 120-min dynamic PET scan centered on the pancreas. One- and 2-tissue-compartment models were used to estimate pancreas and spleen distribution volume. Reference region approaches (spleen as reference) were also investigated. Quantitative PET measures were correlated with clinical outcome measures. Immunohistochemistry was performed to examine colocalization of dopamine receptors with endocrine hormones in HC and T1DM pancreatic tissue. Results: C-peptide release was not detectable in any T1DM individuals, whereas proinsulin was detectable in 3 of 5 T1DM individuals. Pancreas SUV ratio minus 1 (SUVR-1) (20–30 min; spleen as reference region) demonstrated a statistically significant reduction (–36.2%) in radioligand binding (HCs, 5.6; T1DMs, 3.6; P = 0.03). Age at diagnosis correlated significantly with pancreas SUVR-1 (20–30 min) (R2 = 0.67, P = 0.025). Duration of diabetes did not significantly correlate with pancreas SUVR-1 (20–30 min) (R2 = 0.36, P = 0.16). Mean acute C-peptide response to arginine at maximal glycemic potentiation did not significantly correlate with SUVR-1 (20–30 min) (R2 = 0.57, P = 0.05), nor did mean baseline proinsulin (R2 = 0.45, P = 0.10). Immunohistochemistry demonstrated colocalization of dopamine D3 receptor and dopamine D2 receptor in HCs. No colocalization of the dopamine D3 receptor or dopamine D2 receptor was seen with somatostatin, glucagon, or polypeptide Y. In a separate T1DM individual, no immunostaining was seen with dopamine D3 receptor, dopamine D2 receptor, or insulin antibodies, suggesting that loss of endocrine dopamine D3 receptor and dopamine D2 receptor expression accompanies loss of β-cell functional insulin secretory capacity. Conclusion: Thirty-minute scan durations and SUVR-1 provide quantitative outcome measures for 11C-(+)-PHNO, a dopamine D3 receptor–preferring agonist PET radioligand, to differentiate BCM in T1DM and HCs.




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Chile’s Social Unrest: Why It’s Time to Get Serious about a ‘Just’ Transition

4 November 2019

Patrick Schröder

Senior Research Fellow, Energy, Environment and Resources Programme
President Sebastián Piñera’s decision to cancel the COP25 climate negotiations, which Chile was due to host in early December, shows the importance of ensuring the transition to a sustainable world is just.

2019-11-04-Chile-Protests.jpg

Demonstrators march in Santiago, Chile during street protests which erupted over a now suspended hike in metro ticket prices. Photo: Getty Images.

One year ago, during the last annual Conference of Parties (COP) held in Katowice, the Polish government launched a Solidarity and Just Transition Declaration, signed by 56 governments including the UK, making the case for why the green transition must be just.

Three years earlier in 2015, the landmark Paris Agreement also included provisions for a just transition where it stated that the decarbonization process should be ‘Taking into account the imperatives of a just transition of the workforce and the creation of decent work and quality jobs in accordance with nationally defined development priorities’. In practice, however, the concept of a just transition has not yet been implemented and has not been sufficiently considered by governments or corporations around the world.

The social unrest that has erupted in Chile’s capital Santiago over the past month, which has forced the Chilean government to ask to move this year’s COP to Madrid, is a case in point. This discontent clearly shows that climate action cannot be separated from social justice concerns. There has not been a real commitment by governments to ensure a just transition based on social dialogue from the local to the national level. This was seen in France with the gilets jaunes protests in November 2018 – one month after President Emmanuel Macron ended the so-called ‘fortune tax’ and instead introduced taxes on diesel fuel as part of an effort to transition to green energy – and the current situation in Chile has some striking parallels. 

Sustainability transitions are a complex web of political choices and investment decisions which affect countries and societies in many different ways. Questions of social justice are everywhere, but in most cases, poorly understood by decision-makers. For example, although poverty has been reduced significantly over the last decade, Chile has one of the worst rates of inequality in Latin America and the highest Gini index in the OECD. The decisions taken in 2017 to power Metro de Santiago with solar photovoltaics and wind energy are commendable from a climate perspective, however, it led to students and young people protesting against rises in subway fares in October 2019.

They were joined by Chileans who are frustrated with rising living costs and by workers and trade unions struggling with low wages. As reported by the Chilean Human Rights Commission (INDH), so far more than 4,200 people have been arrested and more than 1,300 injured and hospitalized.

Climate negotiations beyond technicalities

This time there is also another important dimension to the protests: social unrest as a reaction to worsening inequality has the potential to derail multilateral cooperation on climate change and other global issues. Since tackling climate change is a race against the clock, the world faces the challenge of addressing both urgency and equity. The world cannot afford delays and needs to move fast but decision-makers need to take time for deliberation and civic participation to avoid rapid and ill-conceived transitions which eventually meet public resistance.

Many technical experts and negotiators, who often unintentionally divorce climate policy and technical discussions about emission reductions from social justice concerns, have been caught by surprise by the cancellation of the negotiations. For this year’s COP, one important focus of the official negotiations are the so-called 'Article 6 Rules' – the accounting mechanisms and modalities for a new form of international interaction on carbon markets and off-setting to ensure carbon markets can support countries in enhancing the ambitions of their stated climate action, known as Nationally Determined Contributions (NDCs). 

What is becoming much more obvious now is that just transitions are at least equally important for achieving NDCs and other long-term mitigation strategies.

In order to meet the 1.5 degree target, stated by the Intergovernmental Panel on Climate Change (IPCC), the world will have to invest an average of around $3 trillion a year over the next three decades in transforming its energy supply systems. But how can we ensure that these investments benefit low-income communities? Will they further increase everyday living costs? The climate finance related discussions focussing on commercially-oriented investments for low-carbon energy systems in most cases only consider the aspect of affordability, but not the other important principles of alternative ‘just’ energy finance, such as good governance, due process, intra-generational equity, spatial equity and financial resilience. Investments to support just transitions need to ensure investments, not only for large energy infrastructure, but also in the jobs, skills and work vital to both adaptation and mitigation.

Just transitions for a circular economy

The just transition concept is also the entry point to broader discussions about inclusive economic transformations, questioning the dominant paradigm of consumerism and ending the wasteful use of critical resources. The current linear economic model of take-make-throw away – in Chile epitomized by the linear extractive model of the mining sector that has contributed to widening inequality – the linear extractive model is not only destructive on the natural environment but also destructive for social cohesion.

In Chile, the commodity boom in copper production – the country accounts for about 30 per cent of the world’s output – and more recently lithium – which is used in batteries for mobile phones, laptops and electric cars – have generated enormous prosperity in Chile. But the wealth has been unequally distributed and has not been used to lay the foundation for raising the overall level of incomes.

A socially embedded and inclusive circular economy can, therefore, be a way forward from the current situation the Latin American country finds itself in. The circular economy was intended to feature prominently during the 25th COP and Chile’s policies – from the Ministry of Environment and Chile's Production Development Corporation (CORFO) – have played an important role in supporting the development of a circular economy, launching in 2018, the first public circular economy programme in Latin America

The government’s support for start-up companies and entrepreneurs to develop inclusive circular economy business models is the right approach to addressing the issues of waste, employment, services for low-income communities and local economic development. These are solutions that need to be scaled up having the potential to reduce Chile’s economic reliance on the dominant extractive model.

As a global community, it is necessary to address the environmental and social objectives equally as not addressing social objectives will become an obstacle in achieving climate mitigation and solving other environmental issues. 

The Chilean protests are a wake-up call and present an opportunity for the global climate change community – which includes governments – to ensure just transitions are implemented in practice.




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Climate Change, Energy Transition, and the Extractive Industries Transparency Initiative (EITI)

Invitation Only Research Event

17 January 2020 - 9:30am to 5:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Climate change and energy transition are re-shaping the extractive sectors, and the opportunities and risks they present for governments, companies and civil society. As the central governance standard in the extractives sector, the EITI has a critical role in supporting transparency in producer countries.

This workshop will bring together experts from the energy and extractives sectors, governance and transparency, and climate risk and financial disclosure initiatives to discuss the role of governance and transparency through the transition. It will consider the appropriate role for the EITI and potential entry points for policy and practice, and the potential for coordination with related transparency and disclosure initiatives. 

Please note attendance is by invitation only.




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Just Circular Economy Transitions in Latin America

Invitation Only Research Event

11 December 2019 - 9:00am to 12 December 2019 - 5:00pm

Montevideo, Uruguay

To identify and promote collaborative opportunities for an inclusive and sustainable circular economy transition at the international level, a clearer understanding and discussions of the potential winners and losers of such a transition is needed. In short, a ‘win-win-win’ vision for the environment, people and the economy, needs to be built and credible pathways to achieving this vision.

This research workshop, organized by Chatham House and UNIDO, will build on previous and ongoing research by Chatham House, and others, to drive forward an inclusive circular economy agenda and promote a just transition from linear to circular economic models. Chatham House, in collaboration with partners, aims to provide a strong evidence base of the opportunities and trade-offs in this transition from linear to circular models by robustly analysing the political economies in key regions in the developing world and engaging with leading stakeholders from governments, international organizations, civil society and the business community.

Latin America is an important geographical region for the circular economy especially in view of the circular bioeconomy and the agenda around inclusiveness. Several countries are beginning to embrace the circular economy concept and related policies. This workshop will bring together circular economy leaders from policy, business and civil society across Latin American countries to identify and discuss challenges, large-scale positive sum opportunities, investment needs, existing alliances and the potential to scale up circular economy practices. The second day of the workshop includes site visits to various circular economy projects in Uruguay.

Attendance at this event is by invitation only. 

Melissa MacEwen

Project Manager, Energy, Environment and Resources Programme




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Promoting a Just Transition to an Inclusive Circular Economy

1 April 2020

Considerations of justice and social equity are as important for the circular economy transition as they are in the contexts of low-carbon transitions and digitalization of the economy. This paper sets out the just transition approach, and its relevance in climate change and energy transition debates.

Patrick Schröder

Senior Research Fellow, Energy, Environment and Resources Programme

2020-04-01-circular-economy.jpg

Residents of Mount Ijen take sulphur at Ijen Crater, Banyuwangi, East Java, on 2 July 2018. Photo: Getty Images.

Summary

  • Many social and political issues have so far been neglected in planning for the circular economy transition. This paper aims to redress this by considering how ‘just transition’ and social equity may be achieved through policy and practice.
  • The prevailing economic model is linear, in that resources are extracted, transformed into products, used, and finally discarded. In contrast, the circular economy recognizes that natural resources are finite, and aims to keep the materials in products in circulation for as long as possible: reusing, repairing, remanufacturing, sharing and recycling. While the concept of the circular economy is largely focused on developing new technologies and businesses to enable keeping materials in circulation, it also includes the notions of ‘designing out’ waste, substituting renewable materials for non-renewable ones, and restoring natural systems.
  • The UN 2030 Agenda demonstrates that environmental, social and economic sustainability objectives cannot be separated. As the links between the environmental issues of climate change, overconsumption of resources and waste generation, and social issues of inequality and the future of work become increasingly obvious, the urgency to connect environmental with social justice is gaining in significance. The language of ‘just transition’ – a transition that ensures environmental sustainability, decent work, social inclusion and poverty eradication – has started to penetrate debates and research on sustainability policy, particularly in the contexts of climate change and low-carbon energy transition.
  • A just transition framework for the circular economy can identify opportunities that reduce waste and stimulate product innovation, while at the same time contributing positively to sustainable human development. And a just transition is needed to reduce inequalities within and between countries, and to ensure that the commitment of the UN Sustainable Development Goals to leave no one behind is fulfilled.
  • It is important to identify the likely impacts on employment as a result of digitalization and industrial restructuring. Combining circular economy policies with social protection measures will be important in order to ensure that the burden of efforts to promote circularity will not fall on the poor through worsening working conditions and health impacts, reduced livelihoods, or job losses. Identifying potential winners and losers through participatory ‘roadmapping’ can help shape effective cooperation mechanisms and partnerships nationally and internationally.
  • Many low- and middle-income countries that rely heavily on ‘linear’ sectors such as mining, manufacturing of non-repairable fast-moving consumer goods, textiles and agriculture, and the export of these commodities to higher-income countries, are likely to be negatively affected by the shift to circularity. These countries will need support from the international community through targeted assistance programmes if international trade in established commodities and manufactures declines in the medium to long term. 
  • International cooperation to create effective and fair governance mechanisms, and policy coordination at regional, national and local levels will play an important role in shaping a just transition. Multilateral technical assistance programmes will need to be designed and implemented, in particular to support low- and middle-income countries.
  • Governments, international development finance institutions and banks are among the bodies beginning to establish circular economy investment funds and programmes. Just transition principles are yet to be applied to many of these new finance mechanisms, and will need to be integrated into development finance to support the circular economy transition.
  • New international cooperation programmes, and a global mechanism to mobilize dedicated support funds for countries in need, will be critical to successful implementation across global value chains. Transparent and accountable institutions will also be important in ensuring that just transition funds reach those affected as intended.




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Facts about English Learners and the NCLB/ESSA Transition in Select States

These fact sheets provide a sketch of key characteristics of the foreign-born and English Learner (EL) populations in select states. The fact sheets look at the demographics of these states, discuss EL student outcomes as measured by standardized tests, and conclude with an overview of state accountability mechanisms that affect ELs under relevant provisions of the Every Student Succeeds Act and predecessor No Child Left Behind Act.




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Revolution and Political Transition in Tunisia: A Migration Game Changer?

With a history of encouraging workers to emigrate to relieve unemployment at home, Tunisia now has 11 percent of its population living abroad. The factors underlying the 2011 revolution that sparked the Arab Spring have also fueled emigration desires for many Tunisians. This country profile explores historical and current trends in Tunisia from colonial settlement to the aftermath of the Arab Spring, and the new focus on migrant rights at home and abroad.




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Egypt: Migration and Diaspora Politics in an Emerging Transit Country

From being a source of labor emigration to the Gulf region to a destination for refugees from Syria, sub-Saharan Africa, and elsewhere, Egypt has long experienced different forms of mobility. This article, which profiles the trends and policies that have shaped Egypt's migration history, focuses on its long-standing use of migration as a soft-power tool to achieve its foreign policy aims and as a safety valve for political discontent.




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Surprise! Transitioning to online teaching

 By Abbe Herzig, AMS Director of Education Many of us are experiencing stress as schools, colleges and universities move instruction out of the classroom. Fortunately, even if distance learning is new to you, it isn’t new, and there is a … Continue reading




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Effects of Metformin, Metformin Plus Rosiglitazone, and Metformin Plus Lifestyle on Insulin Sensitivity and {beta}-Cell Function in TODAY

TODAY Study Group
Jun 1, 2013; 36:1749-1757
TODAY Study




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Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People

OBJECTIVE

The long-term influences of sex hormone administration on insulin sensitivity and incretin hormones are controversial. We investigated these effects in 35 transgender men (TM) and 55 transgender women (TW) from the European Network for the Investigation of Gender Incongruence (ENIGI) study.

RESEARCH DESIGN AND METHODS

Before and after 1 year of gender-affirming hormone therapy, body composition and oral glucose tolerance tests (OGTTs) were evaluated.

RESULTS

In TM, body weight (2.8 ± 1.0 kg; P < 0.01), fat-free mass (FFM) (3.1 ± 0.9 kg; P < 0.01), and waist-to-hip ratio (–0.03 ± 0.01; P < 0.01) increased. Fasting insulin (–1.4 ± 0.8 mU/L; P = 0.08) and HOMA of insulin resistance (HOMA-IR) (2.2 ± 0.3 vs. 1.8 ± 0.2; P = 0.06) tended to decrease, whereas fasting glucose (–1.6 ± 1.6 mg/dL), glucose-dependent insulinotropic polypeptide (GIP) (–1.8 ± 1.0 pmol/L), and glucagon-like peptide 1 (GLP-1) (–0.2 ± 1.1 pmol/L) were statistically unchanged. Post-OGTT areas under the curve (AUCs) for GIP (2,068 ± 1,134 vs. 2,645 ± 1,248 [pmol/L] x min; P < 0.01) and GLP-1 (2,352 ± 796 vs. 2,712 ± 1,015 [pmol/L] x min; P < 0.01) increased. In TW, body weight tended to increase (1.4 ± 0.8 kg; P = 0.07) with decreasing FFM (–2.3 ± 0.4 kg; P < 0.01) and waist-to-hip ratio (–0.03 ± 0.01; P < 0.01). Insulin (3.4 ± 0.8 mU/L; P < 0.01) and HOMA-IR (1.7 ± 0.1 vs. 2.4 ± 0.2; P < 0.01) rose, fasting GIP (–1.4 ± 0.8 pmol/L; P < 0.01) and AUC GIP dropped (2,524 ± 178 vs. 1,911 ± 162 [pmol/L] x min; P < 0.01), but fasting glucose (–0.3 ± 1.4 mg/dL), GLP-1 (1.3 ± 0.8 pmol/L), and AUC GLP-1 (2,956 ± 180 vs. 2,864 ± 93 [pmol/L] x min) remained unchanged.

CONCLUSIONS

In this cohort of transgender persons, insulin sensitivity but also post-OGTT incretin responses tend to increase with masculinization and to decrease with feminization.




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ADA Practice Transitions offering promotional trial for dentists who sign up through March 1

ADA Practice Transitions, a service offered by the ADA focused on helping dentists make the process of joining or leaving a practice successful, is offering a free three-month trial.




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Performance of High-Sensitivity Cardiac Troponin Assays To Reflect Comorbidity Burden and Improve Mortality Risk Stratification in Older Adults With Diabetes

OBJECTIVE

Incorporation of comorbidity burden to inform diabetes management in older adults remains challenging. High-sensitivity cardiac troponins are objective, quantifiable biomarkers that may improve risk monitoring in older adults. We assessed the associations of elevations in high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) with comorbidities and improvements in mortality risk stratification.

RESEARCH DESIGN AND METHODS

We used logistic regression to examine associations of comorbidities with elevations in either troponin (≥85th percentile) among 1,835 participants in the Atherosclerosis Risk in Communities (ARIC) Study with diabetes (ages 67–89 years, 43% male, 31% black) at visit 5 (2011–2013). We used Cox models to compare associations of high cardiac troponins with mortality across comorbidity levels.

RESULTS

Elevations in either troponin (≥9.4 ng/L for hs-cTnI, ≥25 ng/L for hs-cTnT) were associated with prevalent coronary heart disease, heart failure, chronic kidney disease, pulmonary disease, hypoglycemia, hypertension, dementia, and frailty. Over a median follow-up of 6.2 years (418 deaths), both high hs-cTnI and high hs-cTnT further stratified mortality risk beyond comorbidity levels; those with a high hs-cTnI or hs-cTnT and high comorbidity were at highest mortality risk. Even among those with low comorbidity, a high hs-cTnI (hazard ratio [HR] 3.0 [95% CI 1.7, 5.4]) or hs-cTnT (HR 3.3 [95% CI 1.8, 6.2]) was associated with elevated mortality.

CONCLUSIONS

Many comorbidities were reflected by both hs-cTnI and hs-cTnT; elevations in either of the troponins were associated with higher mortality risk beyond comorbidity burden. High-sensitivity cardiac troponins may identify older adults at high mortality risk and be useful in guiding clinical care of older adults with diabetes.




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Can High-Intensity Exercise Improve Your Memory?

Exercise like walking, swimming, and even dancing have been shown to be good for your memory, but the optimal intensity of that exercise has been unclear... until now

-- Read more on ScientificAmerican.com




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9/11, Iraq and the Desensitization of the Victimized

In the days after the attacks of Sept. 11, 2001, with the twin towers vanished from Manhattan's skyline, a poem by W.H. Auden could have been the song of a wounded nation. "September 1, 1939," written on the eve of World War II, seemed eerily prescient:




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Health Care Transition in Adolescents and Young Adults With Diabetes

Michael E. Bowen
Jun 1, 2010; 28:99-106
Feature Articles




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Connecticut Provides Resources to Ease Transition to Kindergarten

These tools encourage school administrators to gather as much information as possible about the students who will be entering kindergarten and the early-learning offerings in their communities.