Natural compounds that can stimulate salivary secretion are of interest in developing treatments for xerostomia, the perception of a dry mouth, that affects between 10 and 30% of the adult and elderly population. Chemesthetic transient receptor potential (TRP) channels are expressed in the surface of the oral mucosa. The TRPV1 agonists capsaicin and piperine have been shown to increase salivary flow when introduced into the oral cavity but the sialogogic properties of other TRP channel agonists have not been investigated. In this study we have determined the influence of different TRP channel agonists on the flow and protein composition of saliva. Mouth rinsing with the TRPV1 agonist nonivamide or menthol, a TRPM8 agonist, increased whole mouth saliva (WMS) flow and total protein secretion compared with unstimulated saliva, the vehicle control mouth rinse or cinnamaldehyde, a TRPA1 agonist. Nonivamide also increased the flow of labial minor gland saliva but parotid saliva flow rate was not increased. The influence of TRP channel agonists on the composition and function of the salivary proteome was investigated using a multi-batch quantitative MS method novel to salivary proteomics. Inter-personal and inter-mouth rinse variation was observed in the secreted proteomes and, using a novel bioinformatics method, inter-day variation was identified with some of the mouth rinses. Significant changes in specific salivary proteins were identified after all mouth rinses. In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and nonsalivary cystatins which was confirmed by immunoassay. This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.

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

After ejaculation, mammalian spermatozoa must undergo a process known as capacitation in order to successfully fertilize the oocyte. Several post-translational modifications occur during capacitation, including sialylation, which despite being limited to a few proteins, seems to be essential for proper sperm-oocyte interaction. Regardless of its importance, to date, no single study has ever identified nor quantified which glycoproteins bearing terminal sialic acid (Sia) are altered during capacitation. Here we characterize sialylation during mouse sperm capacitation. Using tandem MS coupled with liquid chromatography (LC–MS/MS), we found 142 nonreductant peptides, with 9 of them showing potential modifications on their sialylated oligosaccharides during capacitation. As such, N-linked sialoglycopeptides from C4b-binding protein, endothelial lipase (EL), serine proteases 39 and 52, testis-expressed protein 101 and zonadhesin were reduced following capacitation. In contrast, mitochondrial aconitate hydratase (aconitase; ACO2), a TCA cycle enzyme, was the only protein to show an increase in Sia content during capacitation. Interestingly, although the loss of Sia within EL (N62) was accompanied by a reduction in its phospholipase A₁ activity, a decrease in the activity of ACO2 (i.e. stereospecific isomerization of citrate to isocitrate) occurred when sialylation increased (N612). The latter was confirmed by N612D recombinant protein tagged with both His and GFP. The replacement of Sia for the negatively charged Aspartic acid in the N612D mutant caused complete loss of aconitase activity compared with the WT. Computer modeling show that N612 sits atop the catalytic site of ACO2. The introduction of Sia causes a large conformational change in the alpha helix, essentially, distorting the active site, leading to complete loss of function. These findings suggest that the switch from oxidative phosphorylation, over to glycolysis that occurs during capacitation may come about through sialylation of ACO2.

Mallory-Denk-bodies (MDBs) are hepatic protein aggregates associated with inflammation both clinically and in MDB-inducing models. Similar protein aggregation in neurodegenerative diseases also triggers inflammation and NF-B activation. However, the precise mechanism that links protein aggregation to NF-B-activation and inflammatory response remains unclear. Herein we find that treating primary hepatocytes with MDB-inducing agents (N-methylprotoporphyrin (NMPP), protoporphyrin IX (PPIX), or Zinc-protoporphyrin IX (ZnPP)) elicited an IBα-loss with consequent NF-B activation. Four known mechanisms of IBα-loss i.e. the canonical ubiquitin-dependent proteasomal degradation (UPD), autophagic-lysosomal degradation, calpain degradation and translational inhibition, were all probed and excluded. Immunofluorescence analyses of ZnPP-treated cells coupled with 8 M urea/CHAPS-extraction revealed that this IBα-loss was due to its sequestration along with IBβ into insoluble aggregates, thereby releasing NF-B. Through affinity pulldown, proximity biotinylation by antibody recognition, and other proteomic analyses, we verified that NF-B subunit p65, which stably interacts with IBα under normal conditions, no longer binds to it upon ZnPP-treatment. Additionally, we identified 10 proteins that interact with IBα under baseline conditions, aggregate upon ZnPP-treatment, and maintain the interaction with IBα after ZnPP-treatment, either by cosequestering into insoluble aggregates or through a different mechanism. Of these 10 proteins, the nucleoporins Nup153 and Nup358/RanBP2 were identified through RNA-interference, as mediators of IBα-nuclear import. The concurrent aggregation of IBα, NUP153, and RanBP2 upon ZnPP-treatment, synergistically precluded the nuclear entry of IBα and its consequent binding and termination of NF-B activation. This novel mechanism may account for the protein aggregate-induced inflammation observed in liver diseases, thus identifying novel targets for therapeutic intervention. Because of inherent commonalities this MDB cell model is a bona fide protoporphyric model, making these findings equally relevant to the liver inflammation associated with clinical protoporphyria.

Esophageal squamous cell cancer (ESCC) is an aggressive malignancy with poor therapeutic outcomes. However, the alterations in proteins and post-translational modifications (PTMs) leading to the pathogenesis of ESCC remains unclear. Here, we provide the comprehensive characterization of the proteome, phosphorylome, lysine acetylome and succinylome for ESCC and matched control cells using quantitative proteomic approach. We identify abnormal protein and post-translational modification (PTM) pathways, including significantly downregulated lysine succinylation sites in cancer cells. Focusing on hyposuccinylation, we reveal that this altered PTM was enriched on enzymes of metabolic pathways inextricably linked with cancer metabolism. Importantly, ESCC malignant behaviors such as cell migration are inhibited once the level of succinylation was restored in vitro or in vivo. This effect was further verified by mutations to disrupt succinylation sites in candidate proteins. Meanwhile, we found that succinylation has a negative regulatory effect on histone methylation to promote cancer migration. Finally, hyposuccinylation is confirmed in primary ESCC specimens. Our findings together demonstrate that lysine succinylation may alter ESCC metabolism and migration, providing new insights into the functional significance of PTM in cancer biology.

We developed a simple and rapid method to enrich protein N-terminal peptides, in which the protease TrypN is first employed to generate protein N-terminal peptides without Lys or Arg and internal peptides with two positive charges at their N-termini, and then the N-terminal peptides with or without N-acetylation are separated from the internal peptides by strong cation exchange chromatography according to a retention model based on the charge/orientation of peptides. This approach was applied to 20 μg of human HEK293T cell lysate proteins to profile the N-terminal proteome. On average, 1,550 acetylated and 200 unmodified protein N-terminal peptides were successfully identified in a single LC/MS/MS run with less than 3% contamination with internal peptides, even when we accepted only canonical protein N-termini registered in the Swiss-Prot database. Since this method involves only two steps, protein digestion and chromatographic separation, without the need for tedious chemical reactions, it should be useful for comprehensive profiling of protein N-termini, including proteoforms with neo-N-termini.

Cullin RING E3 Ligases (CRLs) ubiquitylate hundreds of important cellular substrates. Here we have assembled and purified the Ankyrin repeat and SOCS Box protein 9 CUL5 RBX2 Ligase (ASB9-CRL) in vitro and show how it ubiquitylates one of its substrates, CKB. CRLs occasionally collaborate with RING between RING E3 ligases (RBRLs) and indeed, mass spectrometry analysis showed that CKB is specifically ubiquitylated by the ASB9-CRL-ARIH2-UBE2L3 complex. Addition of other E2s such as UBE2R1 or UBE2D2 contribute to polyubiquitylation but do not alter the sites of CKB ubiquitylation. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis revealed that CUL5 neddylation allosterically exposes its ARIH2 binding site, promoting high affinity binding, and it also sequesters the NEDD8 E2 (UBE2F) binding site on RBX2. Once bound, ARIH2 helices near the Ariadne domain active site are exposed, presumably relieving its autoinhibition. These results allow us to propose a model of how neddylation activates ASB-CRLs to ubiquitylate their substrates.

Giardia lamblia (G. lamblia) disease is a zoonosis with a-infection rate affecting the general population of the world. Despite the constant possibility of damage due to their own metabolism, G. lamblia have survived and evolved to adapt to various environments. However, research on energy-metabolism conversion in G. lamblia is limited. This study aimed to reveal the dynamic metabolism-conversion mechanism in G. lamblia under sugar starvation by detecting global lysine acetylation and 2-hydroxyisobutyrylation sites combined with quantitative proteome analyses. A total of 2999 acetylation sites on 956 proteins and 8877 2-hydroxyisobutyryl sites on 1546 proteins were quantified under sugar starvation. Integrated Kac and Khib data revealed that modified proteins were associated with arginine biosynthesis, glycolysis/gluconeogenesis, and alanine, aspartate, and glutamate metabolism. These findings suggested that lysine acetylation and 2-hydroxyisobutyrylation were ubiquitous and provided deep insight into the metabolism-conversion mechanism in G. lamblia under sugar starvation. Overall, these results can help understand the biology of G. lamblia infections and reveal the evolution rule from prokaryote to eukaryote.

Gender-smart Procurement: Policies for Driving Change Research paper sysadmin 14 December 2017

Governments should use public procurement policy as a strategic lever to accelerate gender-inclusive economic growth through the application of state spending power.

• Governments need to rethink public procurement policy. They need to use it as a strategic lever to accelerate gender-inclusive economic growth through the application of state spending power, while maintaining rigorous governance standards. Reform of public procurement to make it more gender-inclusive could create a ‘diversity dividend’ through increased job creation and economic growth. Gender-smart procurement policies could also mitigate economic and business risk by rendering supply chains more diverse.
• In 2014, G20 members agreed to reduce the gender gap in the labour market by 25 per cent by 2025. Procurement policy is one of the most powerful tools governments have to achieve this goal. All G20 members, regardless of the differences in their legal frameworks, can implement measures that will increase the ability of women to benefit from procurement policy.
• Public procurement accounts for around one-fifth of global gross domestic product (GDP). It is estimated that women entrepreneurs supply only 1 per cent of this market. Women’s businesses face considerable barriers to accessing procurement tenders and winning procurement contracts. The inadequate design of many procurement processes prevents more inclusive gender outcomes for citizens. Governments should redefine procurement policies to make explicit the requirement that increasing women’s workforce participation, through greater use of female suppliers, is a key objective when selecting bids for procurement contracts.
• Through the use of policy and spending levers, governments can play four primary roles in encouraging procurement from enterprises owned by women, or from businesses committed to promoting female labour participation. These roles are:
  - To direct reforms of government procurement – reviewing procurement policies and practices to ensure sustainable and inclusive procurement;
  - To reduce barriers to women’s participation in the economy – creating the support mechanisms to ensure an environment in which businesses owned by women can flourish;
  - To help scale up gender-smart procurement in the private sector – expanding government’s role in encouraging private companies to spend more of their procurement budgets with women’s businesses; and
  - To encourage increased transparency on the issues – creating and sharing procurement databases and lessons learned, especially at the regional level.
• Companies can also benefit from having more diverse supply chains and volunteering for accreditation schemes. They can start conversations with government about national regulation that encourages diversity in procurement, leading by example.
• The G20 should set measurable and time-bound targets in the area of gender-smart procurement, to build on the momentum of UN reforms and incorporate good practice in supply chain management.

Afonso Dhlakama’s Death Changes the Calculation for Peace Prospects in Mozambique Expert comment sysadmin 4 May 2018

If politicians continue to act in good faith, the death of the opposition leader may be a significant opportunity to finally draw a line under Mozambique’s long war.

The unexpected death of opposition and ex-rebel leader Afonso Dhlakama on 3 May is a game changer for Mozambique’s politics and an almost-completed peace process. The 65-year old Dhlakama, who died of a heart attack, had led Renamo for 38 years and had totally dominated his party. Dhlakama regularly boasted that he was Mozambique’s ‘father of democracy’, despite not allowing competition within his own party, and he leaves a legacy of more than 30 years of struggle, through both armed action and peaceful politics.

A long war

Originally Renamo had been a tool for the white minority regimes of Rhodesia and apartheid South Africa to challenge the socialist Frelimo political party that took power in Mozambique in 1975. But under Dhlakama’s command, by the late 1980s Renamo had become increasingly independent and rooted in Mozambique. After Renamo’s long war with Frelimo ground to a hurting stalemate, a transition led to Mozambique’s first multiparty elections in 1994, and the creation of a new joint army. A ‘pay and scatter’ programme successfully dispersed and reintegrated many thousands of ex-combatants.

But early post-election gains did not translate to lasting peace. Disarmament was a time-limited, technical process, and devoted declining resources and attention to clusters of ex-combatants that failed to disperse. In addition, Dhlakama was allowed to maintain an armed militia under the guise of a presidential guard.

Mounting economic inequality, notably in opposition strongholds such as central Mozambique, saw Renamo made political gains and Dhlakama nearly won the 1999 presidential elections. (Some believe he did.) The result focused Frelimo’s attention on the threat that Renamo posed and, ultimately, a strategy of pursuing total Frelimo domination across the country, culminating in a crushing Frelimo victory at the 2009 elections.

This humiliated and marginalized former Renamo rebels, resulting in Dhlakama ordering their return to targeted armed violence in 2013. Frelimo’s new leader, President Filipe Nyusi, took power in 2015 and sought direct dialogue with Dhlakama. Five rounds of internationally mediated peace talks took place from July to December. Finally, in late December 2016, Dhlakama announced a unilateral truce, which was extended twice and subsequently made indefinite.

New peace talks also started and, in August 2017 and February 2018, President Nyusi and Dhlakama showed the courage to meet in person, near Renamo’s base in central Mozambique, to build up mutual trust and discuss the details of the emerging peace deal – including the demobilization or integration into government security forces for Renamo’s now mostly middle-aged gunmen.

Dhlakama the ‘Big Man’

Dhlakama’s sudden death has fundamentally changed the negotiation dynamics. He never allowed for any serious succession planning, and ensured all key decisions were his and his alone. Renamo had already decided that he would be its presidential candidate for the 2019 national elections.

His party is significantly weakened by his death and unlikely able to fully recover – but needs to try and reach consensus quickly on a successor, as it will also compete in municipal elections in October and was expecting significant gains. There will be a number of contenders to succeed him including from the parliamentary wing, led by his niece Ivone Soares, its secretary general, Manuel Bissopo, and a few others.

But Renamo’s key leverage for now remains some 1,000 middle-aged gunmen in central Mozambique who have been stoically loyal to Dhlakama since the 1980s and who have little respect for the younger generation of professional politicians based in Maputo. Some may be bought off by government offers, others integrated into localised organized crime groups and others into internal Renamo sectarianism. The risk of fragmentation is real.

Renamo’s weakness could also embolden Frelimo hardliners to seek a return to unilateral domination of Mozambique’s political landscape, and to undermine the peace process. That would be a serious tactical mistake by Frelimo, as a lasting deal is close and the death of Dhlakama could actually assist in making this settlement lasting. Dhlakama was quixotic and prone to changing his mind, often influenced by the last person he spoke to – his death potentially introduces greater predictability in negotiations and in any post-deal implementation.

President Nyusi is clearly aware of this as he hailed on state television TVM that Dhlakama was ‘a citizen who has always worked for Mozambique’ and said he was distraught at the news of his death. He stated, ‘I hope that we as Mozambicans can continue to do everything so things do not go down.’ He also addressed Renamo’s support base by saying that ‘[Dhlakama] did everything so that there would be peace. The last time he spoke to me, he said he was not going to miss out anything in peace negotiations.’

Renamo’s gunmen are fatigued and want to retire with dignity but are vulnerable to manipulation and political miscalculation by Mozambican’s positioning politicians. International partners and investors can engage, by emphasizing that sustainable peace is the only pathway to poverty reduction and inclusive economic development.

This includes assisting development and reconciliation projects in areas impacted by the renewed conflict since 2013. Long-term investment for development in Renamo’s key constituencies could help avoid fragmentation at a critical time – faith groups and NGOs may also have a key role to play.

If Mozambique’s politicians continue to act in good faith, the death of Dhlakama may constitute a significant opportunity to finally draw a line under Mozambique’s long war.

Expanding and enhancing the global cyber workforce 17 November 2022 — 5:00PM TO 6:00PM Anonymous (not verified) 5 October 2022 Chatham House and Online

How can we address the cybersecurity workforce shortage and skills gap?

Accelerated digital transformation and heightened geopolitical tensions on the international stage have increased the need for effective cybersecurity practices and policies as well as a skilled workforce. Despite this, the demand for cybersecurity professionals continues to outpace the supply for societies and businesses globally, resulting in a cybersecurity workforce gap.

To ensure that digital transformation is available, safe and beneficial to all, significant efforts are needed to encourage cyber workforce capacity-building and knowledge-sharing at both national and international levels.

This discussion, supported by (ISC)² and the UK Cyber Security Council, will explore how to effectively address the twin challenges of the global cyber workforce shortage and skills gap.

• What are the implications of the global cyber workforce and skills gaps for businesses and societies?

• What shape do these gaps take within society? Where are they most prevalent and how do they vary?

• What is the role of education and private-public partnerships in effectively addressing these gaps?

• How does the UK National Cyber Strategy seek to address these challenges? What are the key lessons from this strategy?

• What other efforts are being made internationally to bridge this gap? What opportunities are there for knowledge-sharing and capacity-building?

• What is the role of diversity, equity and inclusion in tackling these gaps?

As with all members events, questions from the audience drive the conversation. If you are not a member of Chatham House but would still like to attend the event please email Eleanor Macmillan-Fox to enquire about registration.

Read the transcript. 

Russia’s invasion of Ukraine: How it changed the world 21 February 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 1 February 2023 Chatham House and Online

Chatham House experts examine how the world has changed since 24 February 2022.

Russia’s invasion of Ukraine prompted serious soul-searching about European security, what it means to be European and the futures of the two principal protagonists. However, practical questions have developed throughout the war in surprising ways.

Chatham House is producing a multi-author feature reflecting on seven things Russia’s war has changed in the world. The article assesses the impact of the war one year on, the long-term changes this has catalyzed and unpacks why these changes are significant for the future of international affairs.

This event examines key themes with the research directors who authored the piece. Alliances, national resiliency for both Ukraine and Russia and sanctions are examined including the following questions:

• How did the war change Ukraine?

• What alliances have been forged over the past year? 

• How long can ‘fortress Russia’ weather the storm and what has it revealed about Russia’s integration into the international system? 

• What have countries done to mitigate the impact on supply chains and markets? Who, for example, has been most affected by the grain crisis?

• What have we learnt about Vladimir Putin and Volodymyr Zelensky that we didn’t know before 24 February 2022?

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

Linked article: ‘Seven ways Russia’s war on Ukraine has changed the world’, read the featured piece here.

Read the transcript. 

Why Europe must end limbo for Afghans seeking asylum Expert comment Anonymous (not verified) 14 October 2021

With a focus on evacuations from Afghanistan, the situation in Europe is often forgotten as thousands of asylum seekers continue to wait for their cases to be settled.

Following the Taliban’s takeover of Afghanistan, European leaders shared messages to welcome those evacuated, but the reality of European responses to displacement in Afghanistan paints a more contentious picture. 

As of July 2021, 33,325 cases of Afghan asylum applicants were pending in Germany, in France 18,410 people were waiting on a decision, while in Greece the numbers were 13,660. 

Arguably, such numbers are manageable given European states’ size and their functioning asylum systems but, while 56 per cent of Afghans in Europe receive protection status, a large proportion is still in limbo in differing European countries’ asylum systems. 

Europe hosts fewer than ten per cent of the three million UN-registered displaced Afghans globally, as neighbouring countries carry the burden of Afghanistan’s forced displacement: Iran hosts almost one million Afghan refugees and Pakistan 1.5 million, and these numbers double when adding undocumented or Afghan passport holders.
 
But despite these manageable numbers, national authorities in Europe often leave people waiting for months or even years to receive an asylum decision. Deportations to Afghanistan were halted only after the Taliban’s takeover of Kabul and even then there was resistance to this from certain European countries, while Austria suggested setting up ‘deportation centres’ in countries neighbouring Afghanistan. 

Europe remains a fortress

The European Commission’s Draft Action Plan responding to the events in Afghanistan confirmed the willingness of the European Union (EU) to continue returns to non-European ‘third countries’. So Europe remains a fortress, despite pledging support for ‘the safe and orderly departure of foreign nationals and Afghans who wish to leave the country’. 

The wall by Greece at its border with Turkey and Poland’s treatment of Afghan asylum seekers trapped at its border with Belarus illustrate this hardline stance. The president of the European Council Charles Michel and EU Home Affairs Chief Ylva Johansson both confirm the priority is to secure European borders. 

This is further backed up by the European Council’s latest set of Conclusions on Afghanistan which focuses on security and ‘preventing illegal migration’ while avoiding reference to any domestic asylum efforts or the establishment of protection pathways for Afghans. 

This disconnect is not new. At the national level, reports of illegal pushbacks on European land and sea borders alarmingly intensified in 2020 as authorities intercepted and sent migrants back to neighbouring countries without assessing asylum claims. 

At the EU level, development aid to countries such as Afghanistan has long been conditional on their governments’ adherence to the bloc’s migration objectives of preventing asylum seekers from reaching European borders and facilitating the repatriation of those refused asylum in Europe. 

But this latest displacement crisis from Afghanistan exposes clear inconsistencies in European approaches to asylum and humanitarianism. Migration remains a divisive issue in European politics, but European governments must act promptly to support Afghans already residing in their territories alongside establishing robust international commitments.

Time for concrete action

European countries should firstly improve the treatment of those Afghans currently in limbo within their respective asylum systems by expediting pending Afghan asylum applications and family reunification cases, re-examining rejected asylum applications, and facilitating integration.

Secondly, national authorities should not return asylum seekers to Afghanistan or any third countries deemed ‘safe’. For Europe to coordinate evacuations from Afghanistan while simultaneously deporting asylum seekers undermines the international refugee regime and threaten Europe’s global credibility. 

How European security is changing Expert comment LJefferson 10 January 2022

Although migration, economic, health, tech and climate policy are increasingly thought of in terms of security, different issues are taking place in each of these policy areas.

Since the end of the Cold War, debates about security among both academics and policymakers have shifted away from traditional military or state security towards a broader conception of what security is – including, for example, ideas such as ‘human security’.

More recently, there has been a widespread perception of a ‘return of great power competition’ and even renewed fears about great power war – in other words, a resurgence of traditional security debates that many hoped and believed were a thing of the past. At the same time, and especially since the COVID-19 pandemic began in 2020, the concept of ‘security’ has also been increasingly applied to other areas like economic and health policies.

These complex and parallel developments raise a number of difficult questions. First, does the changing way in which the concept of ‘security’ is used – and in particular the way people now increasingly speak of ‘economic security’ and ‘health security’ – reflect a changing reality or rather simply a changing perception of reality? Second, are these changes in the way we think about security helpful or not? In other words, is the redefinition of security that seems to be taking place leading to good policy responses and making citizens more secure, or is it rather unhelpfully ‘securitizing’ policy areas and possibly undermining democracy in the process?

Part of the reason that these questions are difficult to answer is that there are different developments taking place in different policy areas. This article briefly analyses developments in five policy areas: migration policy, economic and trade policy, health policy, technology policy, and climate policy.

The authors argue there are at least three separate developments taking place, though it is often quite difficult to disentangle them – and more than one development may be taking place in each policy area. The analysis focuses on developments in Europe – defined broadly as including countries such as the UK which are outside the European Union (EU) – which may be different from those taking place elsewhere.

Five policy areas, three trends

In migration policy, the clearest development that is taking place, in particular since the so-called ‘refugee crisis’ of 2015, is the militarization of borders in Europe – in particular, the militarization of the EU’s external border.

The removal of borders within Europe was once seen by some as a step towards a borderless world, but since 2015 the EU seems to have concluded that the internal removal of borders requires a much harder external border than was previously the case.

In particular, since the ‘refugee crisis’, the EU has massively invested in Frontex, its border agency, which describes itself as ‘Europe’s first uniformed service’ that ‘helps guarantee free movement without internal borders checks that many of us take for granted’. In short, we are seeing an application to migration policy of military tools, including armed border guards.

Something different seems to be taking place in economic policy. For the last three or four decades since the end of the Cold War, economic policy has been dominated by (neo-)liberal assumptions. But these are now increasingly being challenged and a shift may be taking place away from this macroeconomic paradigm.

The reasons for this are complex – in part, a domestic backlash against this paradigm, particularly from the ‘losers’ or ‘left behind’ (in other words those who have suffered from the distributional consequences of the economic and especially trade policies of the last 30-40 years going back to the ‘neoliberal turn’), and in part a sense among analysts and policymakers that a different set of more protectionist policies are required in order to compete with China as a ‘systemic rival’.

These two different drivers of an economic paradigm shift have become even more tightly connected since the COVID-19 pandemic began in 2020. The pandemic led to both an increased demand for a new economic paradigm and a sense of intensified competition with China and, in the EU, to a lesser extent with the United States.

However, because the set of rules governing economic and in particular trade policy was set during the earlier period of (neo-)liberal hegemony, they restricted the ability of states to pursue what were seen as protectionist policies in order to redistribute and created exceptions only for security reasons. This has created a structural pressure on nation states to present economic policies in terms of security.

Here, however, the EU may be an outlier. During the last few decades, the EU has gone even further than the rest of the world has in creating rules around economic policy – at least internally. In particular, the EU’s fiscal rules may prevent its member states from borrowing to invest and its state aid rules may prevent them from experimenting with new kinds of industrial policy.

Therefore, the EU may be structurally constrained from making the kind of paradigm shift in economic policy that many now think is necessary. In particular, despite the rhetoric about a more ‘geopolitical’ EU, it may be limited in the extent to which it can think of economic policy in terms of security – sometimes to the regret of security establishments, as is the case for debates around 5G, for example.

In health policy, something similar may be happening as in economic policy. During the last three or four decades, health policy has been approached in a rather liberal way. Across Europe, though to different degrees and in different ways, market principles have been introduced into health systems.

In many cases such as the UK, this has involved privatizing what were previously state functions in healthcare. But since the pandemic, there has been a renewed focus on renationalizing or, in the case of the EU, ‘re-regionalizing’ supply chains, in particular for personal protective equipment (PPE) and vaccines, which is presented in terms of ‘health security’. COVID-19 has also reinforced the need to better include pandemic preparedness in national security planning.

A similar trend seems to be taking place in technology policy, which as with health policy is now increasingly viewed in a defensive, protectionist way rather than the liberal way it was previously seen. For example, the production of semiconductors was previously viewed in economic liberal terms – in other words, they should be produced wherever they can be produced most efficiently.

But analysts and policymakers increasingly see technology as central to the competition between China and the United States – or even more broadly between authoritarian states and democracies. As in health policy, there is an increasing focus on a shared approach among allies and on the ‘resilience’ of supply chains for technology. A similar shift is taking place on the management of data flows and the need to think harder – and maybe, be less naive – about the security impact of our online life.

Finally, in climate policy, something different seems to be taking place. Here, there is neither an attempt to apply military tools (notwithstanding the fact some national European militaries as well as NATO are increasingly interested in climate security, for instance regarding the ability to train and fight in altered weather conditions, notably extreme heat) nor a paradigm shift away from liberalism – although some, especially on the left, do question whether it is possible to prevent catastrophic climate change unless we abandon economic liberalism and much of the debate about green investment is closely connected to debates about an economic paradigm shift.

Rather, what is striking is the increasing talk of a ‘climate emergency’ – with its implication of the need to suspend normal democratic decision-making – and of the need to take extraordinary measures to prevent catastrophic climate change. However, for the time being, such rhetoric on climate change is not matched by relevant extraordinary emergency measures.

Across these five policy areas, in other words, there seem to be at least three developments taking place that are reshaping how we think about security in Europe. The difficult question is whether each of these developments is a ‘good’ thing or not, i.e. whether they actually make European citizens more secure in an appropriate way.

In other words, is it a good idea to militarize the EU’s borders, to shift away from the earlier liberal paradigm in economic, health and technology policy and frame the shift in terms of ‘security’, or to invoke an emergency in order to be able to take more drastic measures to prevent climate change?

The limits of securitization theory

One way of thinking about these issues is what academics call ‘securitization’ – the situation when something is identified in rhetoric as an existential threat to some object, specifying a point of no return, that legitimizes the use of extraordinary measures and pushes the issue higher on the political and policy agenda.

The response to COVID-19 can be seen as an example of securitization – the existential threat to human beings but also healthcare systems was used to legitimize lockdowns and social distancing requirements.

Ukraine response reveals Europe’s security is changing Expert comment NCapeling 8 February 2022

Recent events regarding Ukraine show an active UK responding quickly while EU powers deliberate. But pulling ahead of the pack is not the same as leadership.

Britain’s relationship with Ukraine appears to be thriving, with Ukrainian defence journalist Illia Ponomarenko recently tweeting the ‘British are just unstoppable these days’ and that the UK finds itself ‘on the right side of history’ while one Ukrainian wine bar has started offering free drinks to British nationals.

Ponomarenko’s remarks and the wine bar offer – certainly one post-Brexit benefit of having a British passport – are down to the UK decision to send anti-tank weapons to support Ukraine’s forces against a potential Russian attack.

The UK’s quick response was praised by Ponomarenko as being ‘wise enough not to be lured into going the easiest way, which is always the fastest lane straight to hell’ and strikes a clear contrast with that of Germany, whose typically moderated approach to geopolitical tensions went down badly in Kyiv.

The chief of Germany’s navy was forced to resign after saying Russian president Vladimir Putin ‘deserved respect’ and that Ukraine will never win back annexed Crimea. The German government also sought an energy exception to proposed US sanctions, so that gas can continue to flow into Europe.

France’s response was somewhat stronger but rather confusing as Emmanuel Macron initially called for European Union (EU) member states to ‘conduct their own dialogue’ with Russia, seemingly as an alternative to supporting the US-led NATO response.

Risks of a ‘bullying’ Russia

Although positioning himself as the convener of a transatlantic response to the Ukraine crisis brings welcome respite for UK prime minister Boris Johnson from his domestic ‘partygate’ fiasco, he is also reported as saying some world leaders ‘may not appreciate the deteriorating picture on the Ukrainian border, or fully comprehend the risks posed by a bullying Russia’.

One particular image sums up the difference in approach between the UK and the EU, as a flight path shows a British RAF plane flying around Germany before taking a detour over Denmark on route to Ukraine.

Given that Germany later blocked the export of NATO ally Estonia’s weapons to Ukraine, this image gives ‘Global Britain’ advocates a strong symbol of apparent British reliability and resourcefulness in the face of supposed European deliberation and disunity.

But although the UK’s response to the Ukraine crisis has rightly been credited as swift and substantial, it also reveals deeper developments in the current European security landscape as EU countries had worried Britain might choose to become absent post-Brexit.

Losing one of its two main military powers would certainly have been a blow to Europe, particularly as Russia’s threat has grown in recent years, so there will be relief that the Ukraine crisis shows Britain is undoubtedly committed to the region. Now the question for leaders in Paris, Berlin, and Brussels is how to deal with an active Britain committed to Europe but under no obligation to work within EU processes.

The UK already has an interesting network of bilateral and mini-lateral relationships with European allies. Its Joint Expeditionary Force brings together ten European countries – including Scandinavian and Baltic states – and is well-placed to support NATO activities while also remaining flexible and independent. In the past year, the UK worked with Norway in the Arctic region, provided military engineers support to Poland, and worked directly with France and Germany through the E3 grouping – once again bypassing EU institutions.

The UK also brings a unique diplomatic, technology, and intelligence-sharing relationship with the US which is unavoidably important in dealing with the threat from Russia. As the US sees European security through a NATO lens – rather than an EU one – this makes Britain a leading player as one of the few countries meeting its NATO spending commitments.

UK must do more to win trust

But despite such creative partnerships transcending the constraints of Brexit, the UK must do more to win the trust of the EU’s biggest players France and Germany to be a permanent power in the region. And relations with France have deteriorated following disputes over fishing, a lack of cooperation on migrants, and the AUKUS defence technology agreement between the UK, US, and Australia.

When it comes to Germany, the UK must not use the Ukraine crisis as an opportunity for geopolitical point-scoring. There are good historical reasons for Germany’s cautious approach to military engagement, even if these do constrain the country’s response to this challenge.

In dealing with Russia, some members of Germany’s ruling SPD sincerely believe their party’s less confrontational posture was central to de-escalating conflict during the Cold War. And although some historians may dispute that belief, it is still a distinct and more noble motivation for ‘dovishness’ than pure economic self-interest.

Cooperation always requires some compromise on all sides. Germany must accept some level of economic risk if sanctions against Russia are to be meaningful and France has to accept the necessity of the UK and US’s involvement and that the most effective dialogue is unlikely to be achieved through EU institutions.

Meanwhile, the UK must accept some role for the two biggest EU players, particularly as the Normandy Format which includes Russia, Ukraine, France, and Germany has proved productive in the past. And the UK needs to clamp down on its own economic ties with Russia.

Interview: Sviatlana Tsikhanouskaya The World Today mhiggins.drupal 25 May 2022

Belarus’s exiled democratic opposition leader tells Roxanne Escobales about her unexpected political career and President Lukashenka’s wavering support for Putin

Sviatlana Tsikhanouskaya is the face of the Belarusian democratic movement. In 2020, she stood as a presidential candidate against Aliaksandr Lukashenka after her husband, an anti-corruption campaigner and the main opposition candidate, was arrested on the campaign trail and imprisoned. Lukashenka, autocratic ruler of Belarus for more than 30 years, was re-elected. Since then, Sviatlana has lived in exile in Lithuania meeting with western leaders and calling for regime change in her native land. Her husband Sergey remains in prison serving an 18-year sentence.

You have said in the past that there will be no free Belarus without a free Ukraine. How is the fate of the two countries connected?

The Kremlin wants to drag our countries into the past, and we are looking into a future which we want to choose for ourselves. The Kremlin doesn’t recognize Ukraine or Belarus as independent countries – it sees them as part of Russia. While the current regime is in our country, there will be a constant threat of aggression from Russia. But we are absolutely independent countries with our own languages, cultures and so on.

The fate of Belarus depends a lot on the outcome of the war in Ukraine, it is evident. When Ukraine wins – and they definitely will win – it will mean the Kremlin is weak and that Lukashenka is weak. Every day we create multiple points of pressure on the regime from within the country, from outside the country. For countries like Ukraine and Belarus the support of strong democracies is very important.

It is very important for European society to understand that it is not just a war between Russia and Ukraine. It is a war between democratic values and dictatorship on the territory of Ukraine. It is very important for democracy to have a strong voice at the moment.

Recently Lukashenka said the war was taking too long. Do you think he understood what he was getting into when he supported Vladimir Putin by allowing his illegal invasion to be launched from Belarus?

The support between the Kremlin and Lukashenka has always been situational – it is not a real friendship. Lukashenka got huge political and economic support in 2020 after the protests, and now he owes a debt to the Kremlin and had to show his loyalty.

And we see how his rhetoric is changing because the situation in Ukraine is changing. At the beginning Lukashenka always said that, ‘Me and Putin will take Ukraine in three days’, and when this blitzkrieg failed, now he wants to get out of the situation. Now he wants to say, ‘Look, we are for peace. We didn’t have any intention to invade Ukraine.’ He wants to act like he is a peacemaker.

He only cares about his own interest, not his country or its people. He just wants to keep his power.

You have been living in exile in Lithuania for two years, and a lot has happened in that time. What is the state of the Belarusian democratic movement now?

We have been a grassroots movement since the first day. There is no leader who says you have to do this or that. My role is to work on the political level. My task is to go to the European Union, to the United States, and ask for packages to assist civil society. With this technical assistance from our democratic partners, we have managed to build structures in exile, and people in Belarus have managed to build structures inside the country.

Another task of mine is to inspire people, and to explain to the international community what is going on and to show them that Belarus is not just Lukashenka’s regime – it is people who want change.

I communicate with Belarusian people almost every day, especially those who are in the country. We have to keep close ties. It is important to understand how dangerous it is in Belarus to communicate on different channels like Telegram or even to subscribe to some media sources. But people do this. They understand the threats and the consequences, but their energy is still so alive.

We have to keep this energy strong and to give this assurance to people that in case something happens to them, or their families, they will get help from outside. This is how it works.

This struggle has come at a very personal cost to you and your husband, Sergey, who is in prison for his political activities. How is he doing?

I communicate with my husband through his lawyer, who visits him once a week. It has to be short messages because there is no privacy. Our children can send him letters and they receive letters back from him.

There are thousands of people like Sergey, and we have to take care of all of them. The treatment of political prisoners is much worse than criminals because they are like Lukashenka’s personal enemies. That is why it is so important to support human rights organizations who provide lawyers to political prisoners. It is important to fund support for them and for families of political prisoners.

You were a teacher when you took over your husband’s presidential campaign. If you could go back in time, what advice would you give yourself?

I would wish I could have had more confidence. I didn’t have any political experience – I was an ordinary woman and wife, the same as millions of other Belarusians. At the beginning, I didn’t feel confident because I didn’t know about politics. I didn’t know how to communicate with the political leaders of different countries. I was scared.

What motivated you to step into your husband’s shoes?

It was an accidental choice. It was terrible for my husband. But I saw millions of people on the streets, and when you see people standing shoulder to shoulder it inspires you. Every day thousands of people call me who want to help, and I understand that we are not alone. This motivates me.

Also, the fact that thousands of children want to see their mothers and fathers who are in jail gives me strength. When sometimes you think you can’t do this any more because it is so difficult, you think about those who haven’t seen their children for two years. It is awful.

So, every day, you find something that gives you a small energy and it doesn’t let you give up.

Russian imperial mindset must change for real victory Expert comment NCapeling 8 December 2022

The attitude of Russia’s elite – and wider population – to the states which used to constitute the USSR needs to change in order to solve the Russia challenge.

Although the reverberations of Russia’s invasion of Ukraine clearly stretch around the globe, the strongest shocks are – and will continue to be – felt by those countries Moscow used to directly rule.

These countries struggle to shrug off a Soviet legacy as, to varying degrees – linguistically, technologically, culturally, and politically – they bear psychological and physical scars of Russia’s colonial past and its present mentality.

It does not help that these countries lack an appropriate collective descriptor. Over the years there has been ‘Newly Independent States’ – hardly appropriate after 31 years – the now-defunct ‘Commonwealth of Independent States’, the ‘post-Soviet space’ and ‘Former Soviet Union’ which both reference the past, and simply ‘Eurasia’ which is hardly appropriate for either Ukraine or Turkmenistan.

Some of these former ‘colonies’ are as badly governed and as sinister – albeit not as lethal beyond their borders – as Russia itself. Others, most notably the Baltic states, are modern, liberal, affluent societies, but Moscow’s shadow still looms.

There is a strong mindset in most of Russia’s citizens that, because that it used to rule these other countries, it either still has privileged rights over them or they are not real countries at all – but instead historical aberrations to be extinguished.

What is past is gone

As historian Timothy Snyder has noted, whatever the wrongs of Putin’s ‘history-based’ assertions about the ‘return of historic lands’, all historical claims are bunkum anyway. If the past brings validity, almost no land border on earth would be beyond dispute. It is agreements which count, and Russia signed away the other successor states in 1991.

The Russia and Eurasia programme at Chatham House has, for the last 31 years, always taken as a starting position that these countries are as sovereign as any other. This of course this means they can choose to be in Russia’s embrace if they wish. But none do because Russia is insufficiently attractive. Some have better relationships with Moscow than others – mainly the more autocratic ones – but no former slave goes back to their master willingly.

At the recent Chatham House conference Russia’s war: How will it shape the region’s future? (note the avoidance of a specific descriptor), the overwhelming consensus was that Russia must lose, that Ukraine must be reconstructed and planning for that must start now, and that the regional economy is convulsing.

But another key view was that, in Russia, rent seeking and buying loyalty are likely to lead to the separation of the Russian people and the regime, especially as the population ages and young men being sent to die at the front. Putin may still be popular in some places in Russia, but not in others – although popularity can rise and fall fast in Russia. However, few at the conference foresaw the disintegration of Russia any time soon.

With continued skill, determination, and more weaponry, Ukraine may well vanquish Russia on the battlefield, and this remains a necessary pre-requisite for European security. But even a Ukraine victory will not erase malign intent.

The Russian imperial itch is so deeply embedded, it must be excised not just from Russian capability but from the intention and mindset of elites and in the popular imagination. That is hard to achieve when so many believe in it as fervently as a religion – even the Russian Orthodox Church invokes a messianism in Russia’s imperial ‘rights’.

The wider region is suffering

Getting Russians to look upon their neighbours as equals requires widescale self-reassessment in a post-Putin Russia. But, for now, the wider region will surely be looking to simply neuter Russia’s destructive capacities.

Preclinical data have shown that ¹⁶¹Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their ¹⁷⁷Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose–response curves to evaluate differences in relative biological effectiveness in vitro. Methods: CA20948 cell survival was assessed after treatment with [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTATATE (agonist) and with [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay. Cell binding, internalization, and dissociation assays were performed up to 7 d to acquire time-integrated activity coefficients. Separate S values for each type of particle emission (Auger/internal conversion [IC] electrons and β^– particles) were computed via Monte Carlo simulations, while considering spheric cells. Once the absorbed dose to the cell nucleus was calculated, survival curves were fitted to the appropriate linear or linear-quadratic model and corresponding relative biological effectiveness was evaluated. Results: Although the radiopeptide uptake was independent of the radionuclide, [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 delivered a 3.6 and 3.8 times higher dose to the nucleus, respectively, than their ¹⁷⁷Lu-labeled counterparts on saturated receptor binding. This increased nucleus-absorbed dose was mainly due to the additional emission of IC and not Auger electrons by ¹⁶¹Tb. When activity concentrations were considered, both [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 showed a lower survival fraction than did labeling with ¹⁷⁷Lu. When the absorbed dose to the nucleus was considered, no significant difference could be observed between the dose–response curves for [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTATATE. [¹⁶¹Tb]Tb-DOTA-LM3 showed a linear-quadratic dose response, whereas [¹⁶¹Tb]Tb-DOTATATE showed only a linear dose response within the observed dose range, suggesting additional cell membrane damage by Auger electrons. Conclusion: The IC, rather than Auger, electrons emitted by ¹⁶¹Tb resulted in a higher absorbed dose to the cell nucleus and lower clonogenic survival for [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 than for the ¹⁷⁷Lu-labeled analogs. In contrast, [¹⁶¹Tb]Tb-DOTATATE showed no higher dose response than [¹⁷⁷Lu]Lu-DOTATATE, whereas for [¹⁶¹Tb]Tb-DOTA-LM3 an additional quadratic response was observed. Because of this quadratic response, potentially caused by cell membrane damage, [¹⁶¹Tb]Tb-DOTA-LM3 is a more effective radiopeptide than [¹⁶¹Tb]Tb-DOTATATE for labeling with ¹⁶¹Tb.

Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. ⁶⁸Ga-labeled fibroblast activation protein inhibitor ([⁶⁸Ga]Ga-FAPI-04) PET/MRI, [¹⁸F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter’s sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [⁶⁸Ga]Ga-FAPI-04 PET/MRI and [¹⁸F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [⁶⁸Ga]Ga-FAPI-04 change in SUL_peak percentage, where SUL_peak is SUV_peak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [⁶⁸Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SUL_peak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.

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Four U.S. Marines remain hospitalized after an attack near Hamid Karzai International Airport in Kabul, Afghanistan, last month as service members were evacuating foreign nationals and refugees.

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CALGARY, Alberta, Nov. 5, 2024 — Computer Modelling Group Ltd. (CMG) has announced it is collaborating with NVIDIA to further develop and optimize CMG subsurface simulation solutions for increased speed, […]

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TED Fellow and chemosensory researcher Paule Joseph unveils the hidden power of a sense that's too often overlooked: smell. She delves into the science behind smell — from how it evokes memory and emotion to its potential for early disease detection — and advocates for the creation of a baseline test for taste and smell that could open the door to more comprehensive health care.

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I mentioned on FB yesterday how much my cognitive style has changed as a result of my psychology training. One of the readers asked me to say more about how it had changed, so here’s my answer. Hopefully this post will show people how it is possible to dramatically change your cognitive style. – I’m […]

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The core beliefs that cause the most common problems fall into the following 3 categories. These core beliefs commonly underlie depression and anxiety. Helpless Core Beliefs such as: “I’m incompetent” “I’m needy” “I’m weak” “I’m defective, I don’t measure up” “I’m a failure” Unlovable Core Beliefs such as: “I’m unlovable” “I’m different” “I’m bound to […]

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Lisa Duty of The Learning Accelerator, a Rhode Island Department of Education (RIDE) and Highlander Institute funding partner, outlines the Rhode Islands's commitment to a blended learning future. She describes how the state is developing its new five-year strategic plan that's engaging RIDE's Ambas

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