Brexit: Then, now and the future 2 February 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 30 November 2022 Chatham House and Online

How has Britain’s negotiations with the EU set it on a post-EU path?

The Brexit negotiations went down to the wire between the UK and the EU in December 2020. By January 2021, the UK’s departure from the EU had taken place, but the new relationship was by no means stable. The UK and EU have since clashed on trade, migration and the Northern Ireland Protocol which are all left unresolved. 

This year, both sides have had to deal with domestic political instability, Russia’s invasion of Ukraine and a global energy crisis that has changed the dynamics of its relationship. In the years ahead, both sides will need to address shared challenges, from the rise of China and climate change to security on the European continent. 

This discussion includes those who were in the room during the Brexit negotiations, including Michel Barnier’s adviser, to get an inside look on how the UK and EU negotiated Brexit. Combining insight from the new book, Inside the Deal – How the EU Got Brexit Done, with expert analysis the panel assesses where the post-Brexit negotiations are today.

Key questions include:

• What issues in the deal still need to be fixed?

• How has the EU evolved since Brexit?

• How would a future Labour government approach the UK-EU relationship?

• What are the best and worst case scenarios for UK-EU relations in 2030?

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

Read the transcript.

The future of Europe post-Brexit 28 September 2021 — 5:00PM TO 6:00PM Anonymous (not verified) 17 August 2021 Online

In conversation with Michel Barnier, Chief Brexit Negotiator, European Union (2016-2019).

Drawing on the diary he kept during the 1600 days of complex and acrimonious Brexit negotiations, Michel Barnier explores the political and practical implications for Europe post-Brexit.

Britain’s departure from the European Union has been a long and difficult journey. Many questions remain about what future lies ahead for the UK and EU and the relations between them.

• To what extent were UK negotiating positions shaped by politics within the ruling Conservative government? How did domestic politics in EU member states shape EU positions? What were key turning points in the negotiations?
• What are the hopes and expectations for bilateral relations between the UK and EU states?
• What is the scope for UK – EU cooperation on transatlantic issues and relations with China

This event forms part of Chatham House’s ongoing work on Effective Multilateralism.

Read a transcript.

As with all Chatham House member events, questions from members drive the conversation. Attending this event and watching the full event video is for Chatham House members only. Not a member? Find out more.

Tumor hypoxia, an integral biomarker to guide radiotherapy, can be imaged with ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) hypoxia PET. One major obstacle to its broader application is the lack of standardized interpretation criteria. We sought to develop and validate practical interpretation criteria and a dedicated training protocol for nuclear medicine physicians to interpret ¹⁸F-FMISO hypoxia PET. Methods: We randomly selected 123 patients with human papillomavirus–positive oropharyngeal cancer enrolled in a phase II trial who underwent 123 ¹⁸F-FDG PET/CT and 134 ¹⁸F-FMISO PET/CT scans. Four independent nuclear medicine physicians with no ¹⁸F-FMISO experience read the scans. Interpretation by a fifth nuclear medicine physician with over 2 decades of ¹⁸F-FMISO experience was the reference standard. Performance was evaluated after initial instruction and subsequent dedicated training. Scans were considered positive for hypoxia by visual assessment if ¹⁸F-FMISO uptake was greater than floor-of-mouth uptake. Additionally, SUV_max was determined to evaluate whether quantitative assessment using tumor-to-background ratios could be helpful to define hypoxia positivity. Results: Visual assessment produced a mean sensitivity and specificity of 77.3% and 80.9%, with fair interreader agreement ( = 0.34), after initial instruction. After dedicated training, mean sensitivity and specificity improved to 97.6% and 86.9%, with almost perfect agreement ( = 0.86). Quantitative assessment with an estimated best SUV_max ratio threshold of more than 1.2 to define hypoxia positivity produced a mean sensitivity and specificity of 56.8% and 95.9%, respectively, with substantial interreader agreement ( = 0.66), after initial instruction. After dedicated training, mean sensitivity improved to 89.6% whereas mean specificity remained high at 95.3%, with near-perfect interreader agreement ( = 0.86). Conclusion: Nuclear medicine physicians without ¹⁸F-FMISO hypoxia PET reading experience demonstrate much improved interreader agreement with dedicated training using specific interpretation criteria.

EU-Turkey Customs Union: Lessons for Brexit 15 March 2018 — 11:00AM TO 12:00PM Anonymous (not verified) 5 March 2018 Chatham House, London

Turkey and the EU are preparing to open negotiations to modernize their 22 year old customs union and expand its scope beyond goods to include services, public procurement and a more liberal regime for agriculture. At the same time, the UK is debating whether to seek a customs union with the EU to facilitate a frictionless flow of goods and to prevent a hard border with Ireland. The speaker will discuss Turkey’s customs union modernization agenda and share his insights on the lessons for the UK’s future relationship with the EU.

Attendance at this event is by invitation only.

EU-Turkey Customs Union: Prospects for Modernization and Lessons for Brexit 12 December 2018 — 12:30PM TO 1:30PM Anonymous (not verified) 26 November 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Turkey and the EU have been in a customs union since 1995. Both sides recognize that the current agreement is in need of modernization and have agreed to open negotiations to expand its scope to include services, public procurement, agriculture and other elements that would help bring it into the 21st century.

At the same time, the UK Parliament is debating whether to approve the agreement on the UK’s withdrawal from the EU. It includes a backstop which – if triggered – would keep the UK and the EU in a single customs territory which would limit the disruption of withdrawal but hamper Britain’s ability to pursue an independent trade policy. The political declaration proposes building on this customs arrangement as the basis for the future relationship.

In this context, the speaker will discuss the current EU-Turkey customs union arrangement and its shortcomings, examine the prospects for its modernization and share his insights on the lessons for the UK’s future trading relationship with the EU.

The event will launch the briefing paper ‘EU-Turkey Customs Union: Prospects for Modernization and Lessons for Brexit’.

Attendance at this event is by invitation only.

Officials in Mexico and across Latin America are anxiously watching the outcome of Tuesday's U.S. Presidential contest in light of GOP candidate Donald Trump's campaign promise to "deport 11 million criminal aliens."

Lionel Messi said Inter Miami will get ready to "come back stronger next year" after the Herons' upset loss to Atlanta United in the first round of the 2024 MLS Cup playoffs.

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Although common ‘disorders’ (e.g., eating disorders, anxiety, and depression) look different on the surface, there are some common underlying mechanisms. One of these is checking. I’m going to go explain the role of checking in a selection of common mental health problems. Checking in Health Anxiety Examples: – Person goes to the Dr for blood […]

The post CBT: How Checking Contributes to Mental Health Problems (Eating Disorders, Depression, Anxiety) appeared first on Dr Alice Boyes.

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New state mandates start next school year aimed at identifying and supporting students with dyslexia. The 2016 law also led to development of training for teachers.

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Nebraska women’s basketball star Alexis Markowski was named to the Preseason Women’s Top 50 Watch List for the John R. Wooden Award. This news was confirmed on Thursday per a release from the athletic department. The award is given annually to that season's mos

Evdokia Menelaou
Aug 8, 2012; 32:10925-10939
BehavioralSystemsCognitive

Umut Güçlü
Jul 8, 2015; 35:10005-10014
BehavioralSystemsCognitive

α-Neurexins are essential and highly expressed presynaptic cell-adhesion molecules that are frequently linked to neuropsychiatric and neurodevelopmental disorders. Despite their importance, how the elaborate extracellular sequences of α-neurexins contribute to synapse function is poorly understood. We recently characterized the presynaptic gain-of-function phenotype caused by a missense mutation in an evolutionarily conserved extracellular sequence of neurexin-3α (A687T) that we identified in a patient diagnosed with profound intellectual disability and epilepsy. The striking A687T gain-of-function mutation on neurexin-3α prompted us to systematically test using mutants whether the presynaptic gain-of-function phenotype is a consequence of the addition of side-chain bulk (i.e., A687V) or polar/hydrophilic properties (i.e., A687S). We used multidisciplinary approaches in mixed-sex primary hippocampal cultures to assess the impact of the neurexin-3α^A687 residue on synapse morphology, function and ligand binding. Unexpectedly, neither A687V nor A687S recapitulated the neurexin-3α A687T phenotype. Instead, distinct from A687T, molecular replacement with A687S significantly enhanced postsynaptic properties exclusively at excitatory synapses and selectively increased binding to neuroligin-1 and neuroligin-3 without changing binding to neuroligin-2 or LRRTM2. Importantly, we provide the first experimental evidence supporting the notion that the position A687 of neurexin-3α and the N-terminal sequences of neuroligins may contribute to the stability of α-neurexin–neuroligin-1 trans-synaptic interactions and that these interactions may specifically regulate the postsynaptic strength of excitatory synapses.

Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca²⁺-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca²⁺ imaging in vivo [Postnatal Day (P)12–17] and in acute brain slices (P8–12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca²⁺ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca²⁺-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain.

Abnormal neuronal morphological features, such as dendrite branching, axonal branching, and spine density, are thought to contribute to the symptoms of depression and anxiety. However, the role and molecular mechanisms of aberrant neuronal morphology in the regulation of mood disorders remain poorly characterized. Here, we show that neuritin, an activity-dependent protein, regulates the axonal morphology of serotonin neurons. Male neuritin knock-out (KO) mice harbored impaired axonal branches of serotonin neurons in the medial prefrontal cortex and basolateral region of the amygdala (BLA), and male neuritin KO mice exhibited depressive and anxiety-like behaviors. We also observed that the expression of neuritin was decreased by unpredictable chronic stress in the male mouse brain and that decreased expression of neuritin was associated with reduced axonal branching of serotonin neurons in the brain and with depressive and anxiety behaviors in mice. Furthermore, the stress-mediated impairments in axonal branching and depressive behaviors were reversed by the overexpression of neuritin in the BLA. The ability of neuritin to increase axonal branching in serotonin neurons involves fibroblast growth factor (FGF) signaling, and neuritin contributes to FGF-2-mediated axonal branching regulation in vitro. Finally, the oral administration of an FGF inhibitor reduced the axonal branching of serotonin neurons in the brain and caused depressive and anxiety behaviors in male mice. Our results support the involvement of neuritin in models of stress-induced depression and suggest that neuronal morphological plasticity may play a role in controlling animal behavior.

Words offer a unique opportunity to separate the processing mechanisms of object subcomponents from those of the whole object, because the phonological or semantic information provided by the word subcomponents (i.e., sublexical information) can conflict with that provided by the whole word (i.e., lexical information). Previous studies have revealed some of the specific brain regions and temporal information involved in sublexical information processing. However, a comprehensive spatiotemporal neural network for sublexical processing remains to be fully elucidated due to the low temporal or spatial resolutions of previous neuroimaging studies. In this study, we recorded stereoelectroencephalography signals with high spatial and temporal resolutions from a large sample of 39 epilepsy patients (both sexes) during a Chinese character oral reading task. We explored the activated brain regions and their connectivity related to three sublexical effects: phonological regularity (whether the whole character's pronunciation aligns with its phonetic radical), phonological consistency (whether characters with the same phonetic radical share the same pronunciation), and semantic transparency (whether the whole character's meaning aligns with its semantic radical). The results revealed that sublexical effects existed in the inferior frontal gyrus, precentral and postcentral gyri, temporal lobe, and middle occipital gyrus. Additionally, connectivity from the middle occipital gyrus to the postcentral gyrus and from postcentral gyrus to the fusiform gyrus was associated with the sublexical effects. These findings provide valuable insights into the spatiotemporal dynamics of sublexical processing and object recognition in the brain.

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here, we report that bilirubin (BIL)-dependent cell death in the auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated current (I_h), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca²⁺-dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, I_h, and death, compromising audition at the young adult stage in HCN1^+/+, but not in HCN1^–/– genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca²⁺ overload, neuronal death, and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy.

In about four billion years from now, the Milky Way and Andromeda galaxies will crash together Visualization: NASA, ESA, and F. Summers, STScI Simulation credit: NASA, ESA, G. Besla, Columbia University, and R. van der Marel, STScI

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