el

Troponin T Parallels Structural Nerve Damage in Type 2 Diabetes: A Cross-sectional Study Using Magnetic Resonance Neurography

Clinical studies have suggested that changes in peripheral nerve microcirculation may contribute to nerve damage in diabetic polyneuropathy (DN). High-sensitivity troponin T (hsTNT) assays have been recently shown to provide predictive values for both cardiac and peripheral microangiopathy in type 2 diabetes (T2D). This study investigated the association of sciatic nerve structural damage in 3 Tesla (3T) magnetic resonance neurography (MRN) with hsTNT and N-terminal pro-brain natriuretic peptide serum levels in patients with T2D. MRN at 3T was performed in 51 patients with T2D (23 without DN, 28 with DN) and 10 control subjects without diabetes. The sciatic nerve’s fractional anisotropy (FA), a marker of structural nerve integrity, was correlated with clinical, electrophysiological, and serological data. In patients with T2D, hsTNT showed a negative correlation with the sciatic nerve’s FA (r = –0.52, P < 0.001), with a closer correlation in DN patients (r = –0.66, P < 0.001). hsTNT further correlated positively with the neuropathy disability score (r = 0.39, P = 0.005). Negative correlations were found with sural nerve conduction velocities (NCVs) (r = –0.65, P < 0.001) and tibial NCVs (r = –0.44, P = 0.002) and amplitudes (r = –0.53, P < 0.001). This study is the first to show that hsTNT is a potential indicator for structural nerve damage in T2D. Our results indirectly support the hypothesis that microangiopathy contributes to structural nerve damage in T2D.




el

Major Improvement in Wound Healing Through Pharmacologic Mobilization of Stem Cells in Severely Diabetic Rats

Current therapeutic strategies for diabetic foot ulcer (DFU) have focused on developing topical healing agents, but few agents have controlled prospective data to support their effectiveness in promoting wound healing. We tested a stem cell mobilizing therapy for DFU using a combination of AMD3100 and low-dose FK506 (tacrolimus) (AF) in streptozocin-induced type 1 diabetic (T1DM) rats and type 2 diabetic Goto-Kakizaki (GK) rats that had developed peripheral artery disease and neuropathy. Here, we show that the time for healing back wounds in T1DM rats was reduced from 27 to 19 days, and the foot wound healing time was reduced from 25 to 20 days by treatment with AF (subcutaneously, every other day). Similarly, in GK rats treated with AF, the healing time on back wounds was reduced from 26 to 21 days. Further, this shortened healing time was accompanied by reduced scar and by regeneration of hair follicles. We found that AF therapy mobilized and recruited bone marrow–derived CD133+ and CD34+ endothelial progenitor cells and Ym1/2+ M2 macrophages into the wound sites, associated with enhanced capillary and hair follicle neogenesis. Moreover, AF therapy improved microcirculation in diabetic and neuropathic feet in GK rats. This study provides a novel systemic therapy for healing DFU.




el

Retinopathy in a Diet-Induced Type 2 Diabetic Rat Model and Role of Epigenetic Modifications

Type 2 diabetes accounts for 90% of the population with diabetes, and these patients are generally obese and hyperlipidemic. In addition to hyperglycemia, hyperlipidemia is also closely related with diabetic retinopathy. The aim was to investigate retinopathy in a model closely mimicking the normal progression and metabolic features of the population with type 2 diabetes and elucidate the molecular mechanism. Retinopathy was evaluated in rats fed a 45% kcal as fat diet for 8 weeks before administering streptozotocin, 30 mg/kg body weight (T2D), and compared with age- and duration-matched type 1 diabetic rats (T1D) (60 mg/kg streptozotocin). The role of epigenetic modifications in mitochondrial damage was evaluated in retinal microvasculature. T2D rats were obese and severely hyperlipidemic, with impaired glucose and insulin tolerance compared with age-matched T1D rats. While at 4 months of diabetes, T1D rats had no detectable retinopathy, T2D rats had significant retinopathy, their mitochondrial copy numbers were lower, and mtDNA and Rac1 promoter DNA methylation was exacerbated. At 6 months, retinopathy was comparable in T2D and T1D rats, suggesting that obesity exaggerates hyperglycemia-induced epigenetic modifications, accelerating mitochondrial damage and diabetic retinopathy. Thus, maintenance of good lifestyle and BMI could be beneficial in regulating epigenetic modifications and preventing/retarding retinopathy in patients with diabetes.




el

The roots to peace in the Democratic Republic of Congo: conservation as a platform for green development

2 July 2014 , Volume 90, Number 4

Richard Milburn




el

Fossil Fuels Expert Roundtable: Managing Disputes and Arbitrations Involving the Extractive Sector in Africa

Invitation Only Research Event

30 September 2014 - 5:00pm to 6:30pm

Chatham House, London

Event participants

Paula Hodges QC, Partner; Head, Global Arbitration Practice, Herbert Smith Freehills
Stéphane Brabant, Partner; Chairman, Africa Practice Group, Herbert Smith Freehills

Disputes between international companies and national governments commonly arise in the extractive industry where high expectations from producer countries often run alongside emotive issues of ‘ownership’ and ‘exploitation’. In 2013, Chatham House published the report Conflict and Coexistence in the Extractives Industries, examining the rising occurrence of long-running and expensive company-government disputes. Continuing the conversation, the speakers will share their personal insights regarding doing business in Africa's oil and gas sector and preparing for crisis situations. They will outline why they believe the effective management of any crisis is critical to achieving an early settlement and why arbitration is the best formal mechanism for resolving disputes in Africa. They will also discuss what the preconditions of success are, and how companies must adjust to new commercial and political realities when engaging with national companies. 

Attendance at this event is by invitation only.

Owen Grafham

Manager, Energy, Environment and Resources Programme
+44 (0)20 7957 5708




el

Illegal Logging and Related Trade: The Response in Indonesia

29 October 2014

The Indonesian government has taken a number of important steps to tackle illegal logging and the associated trade but  implementation and enforcement challenges remain, in particular a poorly functioning decentralized governance system, persistent corruption and insufficient transparency of information.

Alison Hoare

Senior Research Fellow, Energy, Environment and Resources Programme

Laura Wellesley

Research Fellow, Energy, Environment and Resources Programme

20141027IllegalLoggingIndonesia.jpg

Timber and logging railroad used to transport logs made by illegal loggers at Kerumutan protected tropical rainforest in Riau province, Sumatra, Indonesia. Photo by Getty Images.

This paper is part of a broader Chatham House study which assesses the global response to illegal logging and the related trade.

The Indonesian government has taken a number of important steps to tackle illegal logging and the associated trade, most notably with the ratification of the Indonesia–EU FLEGT voluntary partnership agreement in 2014. The process of negotiating this agreement has contributed to the introduction of a national timber legality verification system (SVLK), clarification of the relevant legal framework and significantly improved engagement with stakeholders in the forest sector. There have also been important developments in recognizing indigenous peoples’ tenure rights to forest land and resources.

However, implementation and enforcement challenges remain. In particular, progress is hampered by a poorly functioning decentralized governance system, persistent corruption and insufficient transparency of information.

The private sector has responded positively, with growing awareness of the issue of illegal logging. While uptake of voluntary legality verification has recently declined, with the need for this now circumvented by the introduction of the SVLK, the area of forest certified as being managed sustainably increased in 2012.

An analysis of data on timber production and consumption suggests that illegal logging has decreased since 2000, and the findings of the expert perceptions survey tend to confirm this for the period 2010 to 2013. In part, these findings reflect a shift towards plantations and away from natural forest harvesting. However, legal ambiguity over the permitting process for forest conversion may mean that levels of illegality are higher than these data suggest.

Building on the government’s response to illegal logging will require effective implementation of the SVLK including addressing identified shortcomings. Improved land-use planning to support effective control and monitoring of forest conversion is also needed. Increased resources and training for enforcement officials are required, while efforts to tackle corruption in the sector should be stepped up. The government should clarify the rights of indigenous peoples through concrete actions such as developing clear processes for mapping and registering their land claims.




el

Illegal Logging and Related Trade: The Response in Brazil

29 October 2014

Brazil's government has made slow progress in tackling illegal logging and associated trade, and illegality, corruption and fraud remain widespread in the country's forest sector, despite a relatively strong legal framework. 

Laura Wellesley

Research Fellow, Energy, Environment and Resources Programme

20141028LoggingBrazilWellesley.jpg

View of a tree in a deforested area in the middle of the Amazon jungle during an overflight by Greenpeace activists over areas of illegal exploitation of timber in the state of Para, Brazil. Photo by Getty Images.

This paper is part of a broader Chatham House study which assesses the global response to illegal logging and the related trade.

The Brazilian government has made slow progress in tackling illegal logging and associated trade since the previous Chatham House assessment, in 2010. Illegality, corruption and fraud remain widespread in the forest sector, despite a relatively strong legal framework. Considerable efforts have been made to improve law enforcement in the sector but these have been hampered by poor coordination between the relevant government agencies, limited resources and inadequate penalties. At the same time, attempts to involve a range of stakeholders in policy discussions and decision-making have stalled.

The private sector’s response to illegal logging is perceived to be weak, despite the reasonably high uptake of sustainability certification schemes. Initiatives are under way aimed at promoting a legal and sustainable market for timber within Brazil, with the engagement of the private sector. However, such undertakings are modest given that the majority of the country’s timber production is consumed domestically.

Considerable investment in systems to monitor timber and revenue flows is required to tackle fraud, while the regulation of sawmills needs to be tightened to reduce the scope for the laundering of illegal timber. The imposition of appropriate sanctions and ensuring the collection of financial penalties could help to fill the gap in resources that is impeding effective enforcement.

Clarification of the regulatory framework is needed – in particular, those regulations related to the fiscal regime for the forest sector – as is the simplification of the processes for approving forest management plans. The latter is a priority if smallholders are to be able to engage in legal and sustainable forest management. An extensive programme of outreach and training is a prerequisite for ensuring such engagement. Finally, efforts to promote legal timber on the domestic market should be intensified and expanded.




el

Illegal Logging and Related Trade: The Response in Ghana

29 October 2014

The Ghanaian government has taken a number of important steps to reduce illegal logging and related trade but a number of enforcement and administrative challenges remain, as well as broader governance challenges including corruption.

Alison Hoare

Senior Research Fellow, Energy, Environment and Resources Programme

20141028LoggingGhanaHoare.jpg

Exotic species of hardwood timber harvested from Ghana's rain forests, at a sawmill in Kumasi, in the Ashanti Region in Ghana. Photo by Getty Images.

This paper is part of a broader Chatham House study which assesses the global response to illegal logging and the related trade. 

The Ghanaian government has taken a number of important steps to reduce illegal logging and related trade, most notably with the signing of the Ghana–EU voluntary partnership agreement in 2009. This agreement has prompted improved multi-stakeholder dialogue within the sector as well as a process of legal reform. Considerable effort has also been put into the development of a timber legality assurance system, which has been successfully piloted. However, a number of enforcement and administrative challenges remain, particularly in relation to tenure and land and resource rights, as well as broader governance challenges including corruption.

Awareness of the issue of illegal logging has improved among the private sector, and the area of natural forest that is verified as legally compliant has increased considerably in recent years. However illegal practices remain widespread in the country. Illegal chainsaw milling is prevalent, predominantly supplying the domestic market. Illegality is also an issue in supply chains for export, albeit at a lower level. Trade data discrepancies indicate that illegal trade is a problem, in particular for tropical logs, and there is a lack of clarity over the legality of many logging permits.

A key challenge for the country is its declining resource base. The forest sector has shrunk considerably over the last 15 years as a result of this, and the situation looks set to worsen. Wood-balance estimates indicate that timber consumption considerably exceeds sustainable harvesting levels. 

In order to make further progress in tackling illegal logging, the process of legal reform and efforts to improve enforcement need to continue. Priorities include: a review of fiscal policies for the sector; improvements to land administration; completion of the conversion process of logging rights; and implementation of the legality assurance system across the country. Efforts must also continue to address the challenge of illegal chainsaw milling, which will require a range of approaches from legal reform to developing alternative livelihood strategies. 




el

Illegal Logging and Related Trade: The Response in Lao PDR

29 October 2014

The government of Lao PDR has taken steps to reduce illegal logging and associated trade but significant implementation and enforcement challenges remain. The country also faces pressure on forest resources from agricultural plantations, mineral extraction and infrastructure development.

Jade Saunders

Associate Fellow, Energy, Environment and Resources Programme

20141028LoggingLaosSaunders.jpg

This aerial picture shows a logging site inside a forest in Boulikhamsai. Photo by Getty Images.

This paper is part of a broader Chatham House study which assesses the global response to illegal logging and the related trade. 

The government of Lao PDR has taken a number of steps to reduce illegal logging and associated trade. Most notably, it has made progress towards negotiations with the EU on a voluntary partnership agreement (VPA). This has prompted the establishment of a multi-stakeholder steering committee and a technical working group and the revision of several land and forestry laws to include provisions related to the Forest Law Enforcement, Governance and Trade (FLEGT) Action Plan.

However, significant implementation and enforcement challenges remain. The legal framework is unclear and, at times, contradictory. Implementation by central and local governments is inconsistent, and internal mechanisms to oversee government decisions are limited. Moreover, enforcement capacity is weak and there is a lack of transparency. The available evidence suggests that illegal practices are widespread in the forest sector.

Awareness of the issue of illegal logging has improved, including in the private sector. The area of natural forest certified under the Forest Stewardship Council (FSC) scheme has been gradually increasing in recent years. However, a key challenge for the Lao forest sector is pressure on forest resources from agricultural plantations, mineral extraction and infrastructure development.

In order to make further progress in tackling illegal logging, the government should push ahead with preparations for the VPA negotiations, ensuring that the lead agencies are appropriately engaged and resourced to implement a credible dialogue process. Data on the allocation and management of forest resources should be systematically collected and made available to the public in order to enable effective forest monitoring. In addition, accountability mechanisms, including anti-corruption strategies, should be clearly defined and implemented by all relevant ministries to ensure that forest resources are exploited legally and for the benefit of the country. 




el

Methodology for Estimating Levels of Illegal Timber- and Paper-sector Imports: Estimates for China, France, Japan, the Netherlands, the UK, the US and Vietnam

25 November 2014

This paper accompanies a series of assessments on China, France, Japan, the Netherlands, the UK, the US and Vietnam, providing details on how the estimates of the level of illegality of imports of wood-based products into those countries were derived.

Alison Hoare

Senior Research Fellow, Energy, Environment and Resources Programme

This paper accompanies a series of Chatham House assessments on China, France, Japan, the Netherlands, the UK, the US and Vietnam and provides details on how the estimates of the level of illegality of imports of wood-based products into those countries were derived. The assessments are part of a research project that monitored levels of illegal logging and related trade in selected consumer, producer and processing countries in order to evaluate the effectiveness of efforts to tackle this problem.

The paper describes the methodology for estimating the levels of wood-based products at high risk of illegality that are being imported into consumer and processing countries. The methodology was developed in order to provide quantitative estimates of the scale of such imports and to assess how they have changed over time. The figures adopted for the assessments are based on the best available evidence; but, given the challenges of quantifying levels of illegal logging and the limited information available for some countries, they should not be regarded as definitive. Rather, they indicate the likely levels of illegality and, perhaps more important, how they may have changed over time.




el

Resource Development in Fragile and Conflict-Affected States: Can it Promote Peace?

Research Event

30 September 2014 - 1:30pm to 4:45pm

Chatham House, London

The discovery of valuable natural resources such as hydrocarbons or minerals in conflict-affected states or disputed regions can be a double-edged sword. While economic growth may help overcome conflict and consolidate peace, much of the academic literature links the economic, social and environmental impacts of resource development with an increased risk of violent conflict between or within fragile states. 

Recently however, the role of business in advancing peace has emerged as a topic of increasing discussion in academia and in forums such as the UN Global Compact. Resource development has also become a key objective for donor development strategies in fragile states such as Afghanistan, Somalia and Myanmar, on the assumption that extractive sector development can contribute to stability and security. 

This event will gather key stakeholders from business and policy to investigate if and where natural resource development has contributed to peace-building, built cooperation among stakeholders or helped to resolve, rather than exacerbate, tensions. If so, it will endeavour to draw out common, replicable lessons of what made these developments successful from a peace-building perspective.

The event will be held under the Chatham House Rule.

Event attributes

Chatham House Rule




el

Cartels and Competition in Minerals Markets: Challenges for Global Governance

19 December 2014

This research paper sets out recommendations for enhanced dialogue and intensified international cooperation that could significantly improve the functioning of global mineral markets.

Felix Preston

Former Senior Research Fellow and Deputy Research Director, Energy, Environment and Resources

Siân Bradley

Research Fellow, Energy, Environment and Resources Programme

Jaakko Kooroshy

Former Chatham House Expert
The purpose of this research paper is to identify and analyse the key policy challenges associated with anti-competitive practices in international metals and minerals markets.

Recommendations

Enhanced dialogue and intensified international cooperation in four areas could significantly improve the functioning of global mineral markets:

  1. Deal with the last remnants of producer-country cartels 
    Consumer countries should make a publicly visible case that in an age of interdependence and global supply chains, any remaining forms of producer-country cartels are an anachronism. Given limited means to coerce governments to stop supporting the last remaining mineral cartels in potash, a ‘naming and shaming’ approach in key forums such as the Group of Twenty (G20) and the Organization for Economic Cooperation and Development (OECD) is likely to be most effective. Such action could be initiated by the three largest potash importers China, India and Brazil, and should seek support from others such as the EU and Japan.
     
  2. Prevent damaging export restrictions through win-win arrangements
    WTO litigation against export restrictions is unlikely to be a silver bullet and in the short term cooperative policy dialogues, such as those pursued by the OECD, offer the best prospects for concrete results. Such dialogues should also be initiated by major emerging economies and could focus on providing incentives such as investment packages or technology-sharing to entice producer countries to abstain from imposing restrictions. Consumers should continue to push for more specific and stricter WTO rules on export restrictions. Japan, the EU and the US should seek to include similar measures in regional trade negotiations.
     
  3. Strengthen cooperation among regulators on clandestine private cartels and other anti-competitive practices 
    Concerted action will be required by governments to tackle anti-competitive practices such as clandestine cartels, price-fixing and territorial agreements. Key regulators, such as those in the EU and China, should expand collection and sharing of data and best practice on anti-trust enforcement in minerals markets. In key cases they could also coordinate prosecution. Sustained investment in institutional capacity is required in many emerging economies; this should be supported through bilateral cooperation and via regional forums. Governments should also resuscitate the stalled negotiations on the WTO’s role in competition policy.
     
  4. Enhance governance for transnational market platforms and pricing mechanisms
    The responsibility to regulate key nodes in global minerals markets will remain in the hands of national bodies, but coordination is vital given interconnected global markets. International organizations and regulators should strengthen structural cooperation and exchange in the area of physical markets and with greater involvement of emerging economies. An informal high-level forum on regulating physical markets could reinvigorate debate, foster new perspectives and stimulate new partnerships. Governments in key consumer countries should also give their national regulators a clear mandate in minerals markets.




el

The Role of Resource Politics in China-US Relations

Research Event

16 January 2015 - 12:00pm to 1:00pm

Chatham House, London

Event participants

Dr David Zweig, Chair Professor, Division of Social Science, Hong Kong University of Science and Technology
Chair: Dr Michal Meidan, Associate Fellow, Asia Programme, Chatham House

China’s resource diplomacy transpires in a world still dominated by the United States. Drawing on extensive research on global energy politics, the speaker will argue that despite Chinese claims that the US is instrumentalizing energy to contain its rise, there is little evidence to suggest that the latter intends to use the ‘oil weapon’.

Department/project

Joshua Webb

+44 (0)20 7314 3678




el

Governance in the DRC: Securing Resources for Development

Invitation Only Research Event

21 January 2015 - 10:30am to 11:30am

Chatham House, London

Event participants

Moïse Katumbi Chapwe, Governor, Katanga Province, Democratic Republic of the Congo

Katanga Province in the Democratic Republic of Congo (DRC) is immensely wealthy in minerals such as copper, uranium and gold, and is home to around fifty per cent of the world’s cobalt reserves. Rising outputs from the province’s copper and cobalt mines have contributed to the DRC’s average GDP growth of 8.5 per cent over the past two years. However, despite visible infrastructure developments in the province to service the industry, few Congolese are benefiting from the revenues and the economy is yet to diversify.

Moïse Katumbi Chapwe, the governor of Katanga Province, will discuss his approach to resource governance and will examine how regional governments can capitalise on resource revenues to improve livelihoods. 

Attendance at this event is by invitation only.




el

Illegal Logging and Related Trade: The Response in Cameroon

21 January 2015

According to this paper, corruption continues to be a dominant feature of Cameroon’s forest sector, and there is an apparent lack of political will to institute change.

Alison Hoare

Senior Research Fellow, Energy, Environment and Resources Programme

20150120LoggingCameroon.jpg

Pallisco logging company's FSC timber operations in Mindourou, Cameroon. Photo by Getty Images.

This paper is part of a broader Chatham House study which assesses the global response to illegal logging and the related trade. 

This assessment of the extent of illegal logging in Cameroon and the response to this issue suggests that progress has stalled since 2010. The reform of the legislative framework for the forest sector has yet to be completed; and while there have been improvements in the availability of forestry information, there remain many gaps. Furthermore, the principle of transparency has yet to be broadly accepted within the government. Enforcement is weak and information management systems are deemed inadequate. Most important, corruption remains widespread and the political will needed to drive change is felt to be lacking.

While there is evidence of progress in the private sector – the area of forests with legality verification and certification has increased – illegal activities are rife throughout the forest sector. Half of all timber production is estimated to come from the informal artisanal sector – mainly supplying the domestic market. However, illegal activities are also common in supply chains for export: timber originating from ‘small permits’ and sales of standing volume permits is thought to be particularly problematic. This is of particular concern, as the supply of timber from such permits is expected to increase owing to the growing pressure on forests from other sectors.

Since 2000 trade has shifted away from sensitive markets: the EU market’s significance as a destination for Cameroon’s exports of timber-sector products has decreased, while China’s significance has increased enormously. This has important implications for strategies on how best to tackle illegal logging in Cameroon.

In order to make further progress, markets for legal timber need to continue to be developed in key consumer countries – which, in the case of Cameroon, are now both the EU and China. Within Cameroon, further analysis of the political economy of the forest sector is required. Attempts to tackle corruption should be reinforced, and this would be facilitated by examining the experience of anti-corruption efforts elsewhere in the world. Further improvements to transparency are needed; the establishment of a new independent observer will be important in achieving this goal.

The next stages of legal reform will require broad consultation among stakeholders, in particular small-scale producers as well as local communities and indigenous peoples. Efforts to promote a legal domestic market should be intensified, including more extensive training and outreach for small-scale producers and processors. Finally, to improve enforcement efforts, continued investment in the training of enforcement agents and the provision of adequate resources are required.




el

Illegal Logging and Related Trade: The Response in Malaysia

21 January 2015

This paper finds high levels of deforestation and widespread problems in Malaysia, particularly in the state of Sarawak.

Alison Hoare

Senior Research Fellow, Energy, Environment and Resources Programme

20150120LoggingMalaysia.jpg

A truck hauls fresh timber from mountainous terrain in the Limbang area of Sarawak, Borneo. Photo by Getty Images.

This paper is part of a broader Chatham House study which assesses the global response to illegal logging and the related trade. 

There has been limited progress in tackling illegal logging and related trade in Malaysia since 2010. Widespread problems remain, particularly in the state of Sarawak. There are high levels of deforestation throughout the country: expansion of timber, pulp and agricultural plantations (including oil palm and rubber) is the main driver of forest loss.

Forest policy-making in Malaysia involves both the federal and state governments, but the states have prerogative rights to develop their own policies on land and forests. This poses challenges, not least since governance of the forest sector varies quite significantly from one region of the country to another.

The government has been negotiating a Voluntary Partnership Agreement (VPA) with the EU since 2007. Negotiations stalled for a number of years but resumed in 2012 without the participation of Sarawak. Concerns remain among stakeholders about the limited recognition of indigenous peoples’ rights by the government, as well as about corruption and the lack of transparency.

Awareness of illegal logging and related trade is increasing in the private sector, although the area of natural forest concessions certified as being under sustainable production remained virtually unchanged during the period 2008–12.

Asia is the major export market destination for Malaysia’s timber products. However, both the US and the EU import significant volumes of wood-based products from Malaysia too.

The Malaysian Anti-Corruption Commission (MACC) has recently stepped up investigating corruption in the forest sector. In Sarawak, an intensified focus on combatting illegal logging could signal a turning point for the state’s forest sector.

In order to build on its response to illegal logging and related trade to date, the Malaysian government should fully engage with the voluntary partnership agreement process and improve multi-stakeholder participation. Transparency in decisions about forest allocation needs to be significantly improved and greater recognition accorded to the rights of indigenous peoples.

More concerted efforts are required to tackle high-level corruption – for example, through strengthening the MACC. At the same time, the government should consider options for an independent monitor for the forest sector as a means of improving forest governance.




el

Estimating Levels of Illegal Logging and the Related Trade: Lessons from the Indicators Project

Invitation Only Research Event

9 November 2015 - 9:00am to 5:00pm

Chatham House, London

The aim of the meeting is to identify ways to improve monitoring of illegal logging and the trade in illegal timber. Building on the experiences of Chatham House’s project Indicators of Illegal Logging, the discussions will focus on the data needs of particular end users and methodological challenges for estimating levels of illegality. The potential for improved coordination and collaboration between global efforts to monitor trade flows will also be considered.

Attendance at this event is by invitation only.

Adelaide Glover

Digital Coordinator, Energy, Environment and Resources Programme




el

The Elements of Power: Gadgets, Guns and the Struggle for a Sustainable Future in the Rare Metal Age

Invitation Only Research Event

19 May 2016 - 5:00pm to 6:30pm

Chatham House, London, UK

At this session, the speaker will argue that our future hinges on a set of elements that receive scant attention even from those whose fortunes rely upon them. The speaker will outline why our electronic gadgets, the most powerful armies and indeed the fate of our planet depend on producing sustainable supplies of rare metals. He will outline some of the  new environmental, economic, and geopolitical consequences of supply chains and discuss the dynamics of the rare metal markets which are vastly different than traditional commodities traded on open exchanges. The speaker will also address some of the security of supply issues arising from China's role as the dominant consumer and producer of most of the world’s minor metals. Finally, the discussion will also include what countries and companies can do to ensure resilient supply lines.

Attendance at this event is by invitation only. 

Owen Grafham

Manager, Energy, Environment and Resources Programme
+44 (0)20 7957 5708




el

Guidelines for Good Governance in Emerging Oil and Gas Producers 2016

13 July 2016

The updated Guidelines focus on eight key objectives for the petroleum sector in emerging producing countries and include policy-oriented recommendations for each objective.

Dr Valérie Marcel

Associate Fellow, Energy, Environment and Resources Programme

2016-07-13-guidelines-good-governance.jpg

An operating drill during oil and gas exploration. Photo: Getty Images.

Summary

The Guidelines for Good Governance in Emerging Oil and Gas Producers 2016, compiled under the auspices of the New Petroleum Producers Discussion Group, review common challenges facing emerging producer countries in the phases of exploration, recent discoveries and early production. The following are the Guidelines’ broad recommendations for addressing these challenges.

  • International best practice may not be appropriate in the case of emerging producers in the oil and gas sector. Instead, the aim should be for more appropriate practice, taking account of the national context; more effective practice, in the interests of achieving rapid results; and better practice, allowing incremental improvements to governance.
  • Government policy should be guided by a clear vision for the development of the country and a strategic view of how the petroleum sector will deliver that vision. 
  • In order to attract the most qualified oil company to a country with an unproven resource base, the host government can invest in geological data, strengthen its prequalification criteria and ensure transparency. It should also plan for success and anticipate the implications of hydrocarbon discoveries in its tax code, and be robust through declining oil and gas prices.
  • Licensing is a key mechanism whereby government can reap early revenues and maximize long-term national benefits. Government must ensure that it simplifies both negotiations and tax structures to mitigate knowledge asymmetries with oil companies.
  • Government and industry must engage and share information with affected communities to manage local expectations regarding the petroleum sector and build trust. 
  • In emerging producers, budgets for local content may be small and timelines for building capacity short. In this context, the focus should be on the potential for repeat use of any local capacity developed. 
  • Meaningful participation of national organizations in resource development is a central objective of many emerging producers. Capacity is needed to enable this, and the Guidelines examine where and how best to develop that capacity.
  • Incremental improvements to the governance of the national petroleum sector will allow emerging producers to increase accountability. The focus in this regard should be on building up capacity in checks and balances as resources become proven.




el

How the New Indonesia-EU FLEGT Licence Can Contribute to the Sustainable Development Agenda

15 November 2016

Alison Hoare

Senior Research Fellow, Energy, Environment and Resources Programme
The FLEGT timber licence marks a breakthrough in the battle against illegal logging and has the potential to help towards achieving the SDGs in the forest sector and beyond.

2016-11-15-Indonesia-logging.jpg

Collected logs along a river in West Kalimantan province, Indonesia. Photo by Getty Images.

Today Indonesia begins issuing the first ever FLEGT licenses for timber exports bound for the EU market. A major step in the battle against illegal logging and trade in illegal timber, these licenses are issued under a national system to verify the legality of all timber and timber products. A commitment to licensing its timber exports to Europe was made in the country’s Voluntary Partnership Agreement (VPA) with the EU, although the licensing system applies to all exports and to the domestic market. The scale of this achievement can not be underestimated given the size of the country and of its forest sector – there are hundreds of thousands of forest enterprises ranging from large-scale concession holders and processing industries, to smallholders and micro-scale loggers, saw-millers and manufacturers.

It is also remarkable given the state of Indonesia’s forest sector at the turn of the century. Looking back to 2000, rule of law was all but absent and corruption was rife - with the allocation of concessions and timber industries closely tied with the country’s ruling elite. Widespread logging contributed to the high rates of deforestation seen at the turn of the century, which stood at over one per cent per year.

In 2016, the forest sector is vastly different – there are much higher levels of accountability and legal compliance, the result of the considerable effort and resources that have been put into enforcement and anti-corruption efforts. The sector is also much more open, reflected both in the significant improvements in the availability of forest data and legislation as well as the increased space that has been made available to civil society to participate both in policy processes and in monitoring of the sector.

These improvements are the result in large part of the reform processes that have been enabled and supported by the VPA process, for which negotiations began in 2007. However, the process is far from complete and the issuance of FLEGT licences is best viewed as a marking point in an ongoing trajectory towards establishing a legal and sustainable sector.

If we take 2000 as the starting point of this trajectory, with FLEGT licensing as the midway point, this brings us to just beyond 2030, the target date for the UN’s global agenda for sustainable development of which the Sustainable Development Goals (SDG) are an integral part. The SDGs provide a broader framework for considering what further progress is needed in the coming years both to improve legality and to ensure that the forest sector makes a positive contribution towards achieving widespread sustainable development in Indonesia.

There are a number of factors that risk the achievement of these aims. Key challenges that remain in the country’s forest sector include the high levels of informality in the small-scale sector, corruption, limited transparency and pressure on forests from other sectors (as highlighted in the report 'Illegal Logging and Related Trade. The Response in Indonesia').

As noted, there are hundreds of thousands of forest enterprises in the country, many of which – particularly small-scale businesses – operate informally. Further concerted efforts are needed to ensure that these enterprises are not excluded from the formal market, but are able to contribute to a thriving economy – for example, through continued support for certification, as well as much greater investment in the provision of extension services and further reforms to establish a policy framework that facilitates the growth of small businesses (see 'Improving Legality Among Small-Scale Forest Enterprises'). This will make an important contribution to the achievement of SDG 8, to enable ‘decent work and economic growth’, this including the target [8.3] to encourage the growth of small enterprises.

Both corruption and limited transparency also need to be addressed if widespread legality and sustainability are to be achieved in the forest sector. Transparency has improved greatly in the forest sector, with significant improvements to the availability of information and the establishment of independent monitoring by civil society. However, further progress is needed to improve the accessibility of information, not least to ensure that NGOs are able to fulfil this monitoring role. In relation to corruption, the anti-corruption agency has made good progress, but it remains under threat and needs to be strengthened. Improving governance is a priority under the SDGs, Goal 16 (peace, justice and strong institutions) including targets to reduce corruption, develop transparent institutions and ensure public access to information.  

The progress made in these areas also needs to be replicated outside the forest sector. A major threat to Indonesia’s forests comes from conversion to other land-uses, in particular agricultural plantations. Effective land-use planning, including transparent and participatory decision-making, is needed if the sustainable management and efficient use of natural resources is to be achieved and deforestation slowed – as set out under SDG 12 (responsible consumption and production) and SDG 15 (life on land).

An important means to drive progress is to ensure close monitoring of progress as well as the evaluation of the measures being adopted. A framework for monitoring the impact of FLEGT licences, as well as the related measures being implemented under the VPA, is under development. This will need to link up to national efforts to monitor progress towards the SDGs – both to contribute towards the monitoring of these goals and to facilitate communication of the progress and lessons being learnt in the forest sector.

To comment on this article, please contact Chatham House Feedback




el

Mining and National Development in the New Global Context

Research Event

1 December 2016 - 5:30pm to 7:00pm

Chatham House, London

Event participants

Tom Butler, Chief Executive Officer, International Council for Mining and Metals (ICMM)
Evelyn Dietsche, Associate Fellow, Energy, Environment and Resources, Chatham House
Chair: Bernice Lee, Executive Director, Hoffman Centre, Chatham House 

During the resources boom of the last decade, countries, companies and communities alike were quick to highlight the transformative potential of the mining sector. With appropriate governance advice and capacity-building support, it seemed the ‘resource curse’ could be overcome. Yet as companies have adjusted their spending in response to declining global commodities prices and longer-term supply and demand projections, low- and middle-income resource-rich economies appear to have increased their dependence on the minerals sector. But how far has the potential of the mining sector been realised to date, and how different does this potential look today?

Taking ICMM’s third edition of the ‘Role of Mining in National Economies’ as the starting point, this meeting will critically assess the contribution that mining has made to development over the past decade, the prospects for ‘mining-led’ growth in the new global context, and the relevance of classic fiscal, employment and governance prescriptions.

Owen Grafham

Manager, Energy, Environment and Resources Programme
+44 (0)20 7957 5708




el

Fossil Fuel Expert Roundtable: Forecasting Forum 2017

Invitation Only Research Event

31 January 2017 - 2:00pm to 5:30pm

Chatham House, London

Presenting latest thinking from our senior research fellows on the dynamics that will affect fossil fuels investment and markets in the year ahead and promoting high-level discussion amongst experts.

The first session examines the oil price market which faces great uncertainty in 2017 with the OPEC agreement in Algiers raising questions about  compliance, supply and impact on the industry's future. It will also assess how US production may alter given the new administration; the state of the nuclear agreement with Iran; and future events in the Middle East.

The second session looks at what Brexit and the election of President Trump means for energy and climate policy in the UK and globally, investigating the major challenges, areas of contention, and areas of opportunity for the UK’s climate and energy policy in light of Brexit.

The second speaker in this session will outline what the appointment of President Trump will mean for global energy and climate policy.

Attendance at this event is by invitation only.




el

A Wider Circle? The Circular Economy in Developing Countries

5 December 2017

Lower-income countries are in many ways more ‘circular’ than their developed-economy counterparts – the question is how to turn this into a development opportunity.

Felix Preston

Former Senior Research Fellow and Deputy Research Director, Energy, Environment and Resources

Johanna Lehne

Former Research Associate, Energy, Environment and Resources

2017-12-05-circular-economy.jpg

A stack of recycled paper ready to be bound into books at a workshop in Kolkata, India. Photo: Felix Preston.

Summary

  • There is growing optimism about the potential of the ‘circular economy’ (CE) as a new model for sustainable growth in developing countries. A CE is one in which products are recycled, repaired or reused rather than thrown away, and in which waste from one process becomes an input into other processes. In recent months there has been CE-related activity in countries as diverse as Laos, Rwanda and Colombia.
  • A CE strategy could help lower-income countries ‘leapfrog’ to a more sustainable development pathway that avoids locking in resource-intensive practices and infrastructure. But a stronger evidence base is needed to show how the agenda can deliver opportunities for industrialization, as well as addressing environmental insecurity.
  • Lower-income countries are in many ways more ‘circular’ than their developed-economy counterparts – the question is how to turn this into a development opportunity. Much economic activity in lower-income countries revolves around sorting and reusing waste. However, higher-value, employment-generating opportunities for reuse and remanufacturing are yet to be captured.
  • The existence of circular activities in developing countries provides excellent political ‘entry points’, which could enable governments, the private sector, civil society and other actors to promote innovative economic models. The CE could provide a powerful narrative, helping to build momentum around a set of ideas that can be applied in and tailored to multiple sectors or cities.
  • There is a window of opportunity in which to align the efforts of development organizations and partner countries. Donors are exploring how the agenda should be aligned with the Sustainable Development Goals (SDGs) and the Paris Climate Agreement. Wider international cooperation on the CE could involve trade partnerships, regional hubs or pilot zones.




el

Reloaded D-backs team set for new season

The D-backs will work to compete in 2019 while continuing to build up the farm system, which has some pitching at the top end with better position players at the lower levels.




el

Kelly already knows his way around ST facility

Yes, catcher Carson Kelly is new to the D-backs this spring, but this wasn't the first time he's gotten to see what the inside of Salt River Fields looks like.




el

'Campfire drill' helps pitchers, catchers bond

After seeing improved communication between pitchers and catchers last year, the "campfire" drill was put back on the D-backs' schedule and took place Friday at Salt River Fields.




el

Adil El-Tayar: renowned NHS transplant surgeon who died from covid-19

bmj;369/may07_6/m1803/FAF1faPhoto credit: Abbas GhazanfarOn 25 March Adil El-Tayar, a renowned organ transplantation specialist, became the first working NHS surgeon to die from covid-19 in hospital...




el

Covid-19: Health needs of sex workers are being sidelined, warn agencies

Agencies have criticised the lack of action to protect the health needs of sex workers during the pandemic, with the English Collective of Prostitutes (ECP) warning of a “ticking time bomb of health...




el

First Evidence for a Dose-Response Relationship in Patients Treated with 166Ho Radioembolization: A Prospective Study

166Ho-microspheres have recently been approved for clinical use for hepatic radioembolization in the European Union. The aim of this study was to investigate the absorbed dose–response relationship and its association with overall survival for 166Ho radioembolization in patients with liver metastases. Methods: Patients treated in the HEPAR I and II studies who underwent an 18F-FDG PET/CT scan at baseline, a posttreatment 166Ho SPECT/CT scan, and another 18F-FDG PET/CT scan at the 3-mo follow-up were included for analysis. The posttreatment 166Ho-microsphere activity distributions were estimated with quantitative SPECT/CT reconstructions using a quantitative Monte Carlo–based method. The response of each tumor was based on the change in total lesion glycolysis (TLG) between baseline and follow-up and was placed into 1 of 4 categories, according to the PERCIST criteria, ranging from complete response to progressive disease. Patient-level response was grouped according to the average change in TLG per patient. The absorbed dose–response relationship was assessed using a linear mixed model to account for correlation of tumors within patients. Median overall survival was compared between patients with and without a metabolic liver response, using a log-rank test. Results: Thirty-six patients with a total of 98 tumors were included. The relation between tumor-absorbed dose and both tumor-level and patient-level response was explored. At a tumor level, a significant difference in geometric mean absorbed dose was found between complete response (232 Gy; 95% confidence interval [CI], 178–303 Gy; n = 32) and stable disease (147 Gy; 95% CI, 113–191 Gy; n = 28) (P = 0.01) and between complete response and progressive disease (117 Gy; 95% CI, 87–159 Gy; n = 21) (P = 0.0008). This constitutes a robust absorbed dose–response relationship. At a patient level, a significant difference was found between patients with complete or partial response (210 Gy; 95% CI, 161–274 Gy; n = 13) and patients with progressive disease (116 Gy; 95% CI, 81–165 Gy; n = 9) (P = 0.01). Patients were subsequently grouped according to their average change in TLG. Patients with an objective response (complete or partial) exhibited a significantly higher overall survival than nonresponding patients (stable or progressive disease) (median, 19 mo vs. 7.5 mo; log-rank, P = 0.01). Conclusion: These results confirm a significant absorbed dose–response relationship in 166Ho radioembolization. Treatment response is associated with a higher overall survival.




el

Multimodality Imaging of Inflammation and Ventricular Remodeling in Pressure-Overload Heart Failure

Inflammation contributes to ventricular remodeling after myocardial ischemia, but its role in nonischemic heart failure is poorly understood. Local tissue inflammation is difficult to assess serially during pathogenesis. Although 18F-FDG accumulates in inflammatory leukocytes and thus may identify inflammation in the myocardial microenvironment, it remains unclear whether this imaging technique can isolate diffuse leukocytes in pressure-overload heart failure. We aimed to evaluate whether inflammation with 18F-FDG can be serially imaged in the early stages of pressure-overload–induced heart failure and to compare the time course with functional impairment assessed by cardiac MRI. Methods: C57Bl6/N mice underwent transverse aortic constriction (TAC) (n = 22), sham surgery (n = 12), or coronary ligation as an inflammation-positive control (n = 5). MRI assessed ventricular geometry and contractile function at 2 and 8 d after TAC. Immunostaining identified the extent of inflammatory leukocyte infiltration early in pressure overload. 18F-FDG PET scans were acquired at 3 and 7 d after TAC, under ketamine-xylazine anesthesia to suppress cardiomyocyte glucose uptake. Results: Pressure overload evoked rapid left ventricular dilation compared with sham (end-systolic volume, day 2: 40.6 ± 10.2 μL vs. 23.8 ± 1.7 μL, P < 0.001). Contractile function was similarly impaired (ejection fraction, day 2: 40.9% ± 9.7% vs. 59.2% ± 4.4%, P < 0.001). The severity of contractile impairment was proportional to histology-defined myocardial macrophage density on day 8 (r = –0.669, P = 0.010). PET imaging identified significantly higher left ventricular 18F-FDG accumulation in TAC mice than in sham mice on day 3 (10.5 ± 4.1 percentage injected dose [%ID]/g vs. 3.8 ± 0.9 %ID/g, P < 0.001) and on day 7 (7.8 ± 3.7 %ID/g vs. 3.0 ± 0.8 %ID/g, P = 0.006), though the efficiency of cardiomyocyte suppression was variable among TAC mice. The 18F-FDG signal correlated with ejection fraction (r = –0.75, P = 0.01) and ventricular volume (r = 0.75, P < 0.01). Western immunoblotting demonstrated a 60% elevation of myocardial glucose transporter 4 expression in the left ventricle at 8 d after TAC, indicating altered glucose metabolism. Conclusion: TAC induces rapid changes in left ventricular geometry and contractile function, with a parallel modest infiltration of inflammatory macrophages. Metabolic remodeling overshadows inflammatory leukocyte signal using 18F-FDG PET imaging. More selective inflammatory tracers are requisite to identify the diffuse local inflammation in pressure overload.




el

Theranostics Targeting Fibroblast Activation Protein in the Tumor Stroma: 64Cu- and 225Ac-Labeled FAPI-04 in Pancreatic Cancer Xenograft Mouse Models

Fibroblast activation protein (FAP), which promotes tumor growth and progression, is overexpressed in cancer-associated fibroblasts of many human epithelial cancers. Because of its low expression in normal organs, FAP is an excellent target for theranostics. In this study, we used radionuclides with relatively long half-lives, 64Cu (half-life, 12.7 h) and 225Ac (half-life, 10 d), to label FAP inhibitors (FAPIs) in mice with human pancreatic cancer xenografts. Methods: Male nude mice (body weight, 22.5 ± 1.2 g) were subcutaneously injected with human pancreatic cancer cells (PANC-1, n = 12; MIA PaCa-2, n = 8). Tumor xenograft mice were investigated after the intravenous injection of 64Cu-FAPI-04 (7.21 ± 0.46 MBq) by dynamic and delayed PET scans (2.5 h after injection). Static scans 1 h after the injection of 68Ga-FAPI-04 (3.6 ± 1.4 MBq) were also acquired for comparisons using the same cohort of mice (n = 8). Immunohistochemical staining was performed to confirm FAP expression in tumor xenografts using an FAP-α-antibody. For radioligand therapy, 225Ac-FAPI-04 (34 kBq) was injected into PANC-1 xenograft mice (n = 6). Tumor size was monitored and compared with that of control mice (n = 6). Results: Dynamic imaging of 64Cu-FAPI-04 showed rapid clearance through the kidneys and slow washout from tumors. Delayed PET imaging of 64Cu-FAPI-04 showed mild uptake in tumors and relatively high uptake in the liver and intestine. Accumulation levels in the tumor or normal organs were significantly higher for 64Cu-FAPI-04 than for 68Ga-FAPI-04, except in the heart, and excretion in the urine was higher for 68Ga-FAPI-04 than for 64Cu-FAPI-04. Immunohistochemical staining revealed abundant FAP expression in the stroma of xenografts. 225Ac-FAPI-04 injection showed significant tumor growth suppression in the PANC-1 xenograft mice, compared with the control mice, without a significant change in body weight. Conclusion: This proof-of-concept study showed that 64Cu-FAPI-04 and 225Ac-FAPI-04 could be used in theranostics for the treatment of FAP-expressing pancreatic cancer. α-therapy targeting FAP in the cancer stroma is effective and will contribute to the development of a new treatment strategy.




el

Prostate-Specific Membrane Antigen PET/CT Combined with Sentinel Node Biopsy for Primary Lymph Node Staging in Prostate Cancer

Our objective was to determine the diagnostic capabilities of combined prostate-specific membrane antigen (PSMA) PET/CT and sentinel node (SN) biopsy in PSMA PET/CT–negative patients for primary lymph node (LN) staging in prostate cancer (PCa) patients. Methods: Between January 2017 and March 2019, retrospectively, all consecutive patients with diagnosed intermediate- or high-risk primary PCa who underwent preoperative PSMA PET/CT (68Ga or 18F-DCFPyL) followed by robot-assisted radical prostatectomy and extended pelvic LN dissection (ePLND) were included. All patients without suspected LN metastases on PSMA PET/CT were considered candidates for SN biopsy with indocyanine green–99mTc-nanocolloid or 99mTc-nanocolloid with free indocyanine green used as tracers. The ePLND was used as a reference standard. Results: Of 53 patients, 22 had positive PSMA PET/CT results and 31 underwent subsequent SN biopsy after negative PSMA PET/CT results. In total, 23 patients (43%) were pN1, of whom 6 (26%) had negative PSMA PET/CT results and underwent subsequent SN biopsy. The combined use of SN biopsy and PSMA PET/CT identified all pN1 patients (100% sensitivity; 95% confidence interval, 86%–100%) and performed correct nodal staging in 50 of 53 patients (94% diagnostic accuracy; 95% confidence interval, 84%–99%). SN biopsy identified significantly smaller LN metastases (median diameter, 2.0 mm; interquartile range, 1.0–3.8 mm) than PSMA PET/CT (median diameter, 5.5 mm; interquartile range, 2.6–9.3 mm; P = 0.007). Conclusion: Combining both modalities led to a 94% accuracy for nodal staging in diagnosed intermediate- and high-risk primary PCa. Adding SN biopsy in patients with negative PSMA PET/CT results increased the combined sensitivity to 100% for detecting nodal metastases at ePLND. This diagnostic accuracy may provide valuable information for directing further treatment in PCa patients, such as the use of PSMA PET/CT and SN biopsy rather than ePLND as the preferred approach for staging before radiotherapy.




el

First-in-Humans Imaging with 89Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of 89Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. Methods: The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of 89Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1–2, 6–8, 24, 48, and 96–144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Results: 89Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time–activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24–48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most 89Zr-IAB22M2C–positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Conclusion: 89Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell–rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.




el

18F-FET PET Imaging in Differentiating Glioma Progression from Treatment-Related Changes: A Single-Center Experience

In glioma patients, differentiation between tumor progression (TP) and treatment-related changes (TRCs) remains challenging. Difficulties in classifying imaging alterations may result in a delay or an unnecessary discontinuation of treatment. PET using O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) has been shown to be a useful tool for detecting TP and TRCs. Methods: We retrospectively evaluated 127 consecutive patients with World Health Organization grade II–IV glioma who underwent 18F-FET PET imaging to distinguish between TP and TRCs. 18F-FET PET findings were verified by neuropathology (40 patients) or clinicoradiologic follow-up (87 patients). Maximum tumor-to-brain ratios (TBRmax) of 18F-FET uptake and the slope of the time–activity curves (20–50 min after injection) were determined. The diagnostic accuracy of 18F-FET PET parameters was evaluated by receiver-operating-characteristic analysis and 2 testing. The prognostic value of 18F-FET PET was estimated using the Kaplan–Meier method. Results: TP was diagnosed in 94 patients (74%) and TRCs in 33 (26%). For differentiating TP from TRCs, receiver-operating-characteristic analysis yielded an optimal 18F-FET TBRmax cutoff of 1.95 (sensitivity, 70%; specificity, 71%; accuracy, 70%; area under the curve, 0.75 ± 0.05). The highest accuracy was achieved by a combination of TBRmax and slope (sensitivity, 86%; specificity, 67%; accuracy, 81%). However, accuracy was poorer when tumors harbored isocitrate dehydrogenase (IDH) mutations (91% in IDH-wild-type tumors, 67% in IDH-mutant tumors, P < 0.001). 18F-FET PET results correlated with overall survival (P < 0.001). Conclusion: In our neurooncology department, the diagnostic performance of 18F-FET PET was convincing but slightly inferior to that of previous reports.




el

Diagnostic Accuracy of PET Tracers for the Differentiation of Tumor Progression from Treatment-Related Changes in High-Grade Glioma: A Systematic Review and Metaanalysis

Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%–92%) and 84% (95% confidence interval, 69%–93%), respectively. O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%–95%) and specificity of 85% (95% confidence interval, 71%–93%). For S-11C-methyl)-l-methionine (11C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%–98%) and specificity was 82% (95% confidence interval, 68%–91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%–100% and 0%–100%, respectively, for 18F-FLT; 85%–100% and 72%–100%, respectively, for 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA); and 100% and 70%–88%, respectively, for 11C-choline. Conclusion: 18F-FET and 11C-MET, both amino-acid tracers, showed a comparably higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.




el

Patient Travel Concerns After Treatment with 177Lu-DOTATATE




el

Fibrotic Encapsulation Is the Dominant Source of Continuous Glucose Monitor Delays

Continuous glucose monitor (CGM) readings are delayed relative to blood glucose, and this delay is usually attributed to the latency of interstitial glucose levels. However, CGM-independent data suggest rapid equilibration of interstitial glucose. This study sought to determine the loci of CGM delays. Electrical current was measured directly from CGM electrodes to define sensor kinetics in the absence of smoothing algorithms. CGMs were implanted in mice, and sensor versus blood glucose responses were measured after an intravenous glucose challenge. Dispersion of a fluorescent glucose analog (2-NBDG) into the CGM microenvironment was observed in vivo using intravital microscopy. Tissue deposited on the sensor and nonimplanted subcutaneous adipose tissue was then collected for histological analysis. The time to half-maximum CGM response in vitro was 35 ± 2 s. In vivo, CGMs took 24 ± 7 min to reach maximum current versus 2 ± 1 min to maximum blood glucose (P = 0.0017). 2-NBDG took 21 ± 7 min to reach maximum fluorescence at the sensor versus 6 ± 6 min in adipose tissue (P = 0.0011). Collagen content was closely correlated with 2-NBDG latency (R = 0.96, P = 0.0004). Diffusion of glucose into the tissue deposited on a CGM is substantially delayed relative to interstitial fluid. A CGM that resists fibrous encapsulation would better approximate real-time deviations in blood glucose.




el

A Critical Insulin TCR Contact Residue Selects High-Affinity and Pathogenic Insulin-Specific T Cells

Type 1 diabetes is an autoimmune-mediated disease that culminates in the targeted destruction of insulin-producing β-cells. CD4 responses in NOD mice are dominated by insulin epitope B:9-23 (InsB9-23) specificity, and mutation of the key T-cell receptor (TCR) contact residue within the epitope prevents diabetes development. However, it is not clear how insulin self-antigen controls the selection of autoimmune and regulatory T cells (Tregs). Here we demonstrate that mutation of insulin epitope results in escape of highly pathogenic T cells. We observe an increase in antigen reactivity, clonality, and pathogenicity of insulin-specific T cells that develop in the absence of cognate antigen. Using a single TCR system, we demonstrate that Treg development is greatly diminished in mice with the Y16A mutant epitope. Collectively, these results suggest that the tyrosine residue at position 16 is necessary to constrain TCR reactivity for InsB9-23 by both limiting the development of pathogenic T cells and supporting the selection of Tregs.




el

A Hybrid Insulin Epitope Maintains High 2D Affinity for Diabetogenic T Cells in the Periphery

β-Cell antigen recognition by autoreactive T cells is essential in type 1 diabetes (T1D) pathogenesis. Recently, insulin hybrid peptides (HIPs) were identified as strong agonists for CD4 diabetogenic T cells. Here, using BDC2.5 transgenic and NOD mice, we investigated T-cell recognition of the HIP2.5 epitope, which is a fusion of insulin C-peptide and chromogranin A (ChgA) fragments, and compared it with the WE14 and ChgA29–42 epitopes. We measured in situ two-dimensional affinity on individual live T cells from thymus, spleen, pancreatic lymph nodes, and islets before and after diabetes. Although preselection BDC2.5 thymocytes possess higher affinity than splenic BDC2.5 T cells for all three epitopes, peripheral splenic T cells maintained high affinity only to the HIP2.5 epitope. In polyclonal NOD mice, a high frequency (~40%) of HIP2.5-specific islet T cells were identified at both prediabetic and diabetic stages comprising two distinct high- and low-affinity populations that differed in affinity by 100-fold. This high frequency of high- and low-affinity HIP2.5 T cells in the islets potentially represents a major risk factor in diabetes pathogenesis.




el

{beta}-Cell Stress Shapes CTL Immune Recognition of Preproinsulin Signal Peptide by Posttranscriptional Regulation of Endoplasmic Reticulum Aminopeptidase 1

The signal peptide of preproinsulin is a major source for HLA class I autoantigen epitopes implicated in CD8 T cell (CTL)–mediated β-cell destruction in type 1 diabetes (T1D). Among them, the 10-mer epitope located at the C-terminal end of the signal peptide was found to be the most prevalent in patients with recent-onset T1D. While the combined action of signal peptide peptidase and endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) is required for processing of the signal peptide, the mechanisms controlling signal peptide trimming and the contribution of the T1D inflammatory milieu on these mechanisms are unknown. Here, we show in human β-cells that ER stress regulates ERAP1 gene expression at posttranscriptional level via the IRE1α/miR-17-5p axis and demonstrate that inhibition of the IRE1α activity impairs processing of preproinsulin signal peptide antigen and its recognition by specific autoreactive CTLs during inflammation. These results underscore the impact of ER stress in the increased visibility of β-cells to the immune system and position the IRE1α/miR-17 pathway as a central component in β-cell destruction processes and as a potential target for the treatment of autoimmune T1D.




el

Maternal Type 1 Diabetes Reduces Autoantigen-Responsive CD4+ T Cells in Offspring

Autoimmunity against pancreatic β-cell autoantigens is a characteristic of childhood type 1 diabetes (T1D). Autoimmunity usually appears in genetically susceptible children with the development of autoantibodies against (pro)insulin in early childhood. The offspring of mothers with T1D are protected from this process. The aim of this study was to determine whether the protection conferred by maternal T1D is associated with improved neonatal tolerance against (pro)insulin. Consistent with improved neonatal tolerance, the offspring of mothers with T1D had reduced cord blood CD4+ T-cell responses to proinsulin and insulin, a reduction in the inflammatory profile of their proinsulin-responsive CD4+ T cells, and improved regulation of CD4+ T cell responses to proinsulin at 9 months of age, as compared with offspring with a father or sibling with T1D. Maternal T1D was also associated with a modest reduction in CpG methylation of the INS gene in cord blood mononuclear cells from offspring with a susceptible INS genotype. Our findings support the concept that a maternal T1D environment improves neonatal immune tolerance against the autoantigen (pro)insulin.




el

Artificial intelligence versus clinicians: systematic review of design, reporting standards, and claims of deep learning studies




el

Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal




el

Use of electronic medical records in development and validation of risk prediction models of hospital readmission: systematic review




el

Prospective registration and reporting of trial number in randomised clinical trials: global cross sectional study of the adoption of ICMJE and Declaration of Helsinki recommendations




el

Estimated population wide benefits and risks in China of lowering sodium through potassium enriched salt substitution: modelling study




el

Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study




el

Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis




el

Playa to cut Jamaican room count 40% with sale of two Jewels

The sale of two Jewel properties will inject US$60 million into loss-making Playa Resorts while reducing the hotel rooms it operates in Jamaica by more 40 per cent. Playa announced the sale of Jewel Runaway Bay Beach Resort...




el

Digital Jamaica throws sales lifeline to furniture companies

DESPITE TUMBLING sales and challenges with hire-purchase accounts, two of the largest retailers of home furniture and appliances, Courts Jamaica and Singer Jamaica, have found glimmers of hope during the COVID-19 pandemic. That’s because work-from...