The greater implications of Bartelson’s Becoming International

Of all major International Relations (IR) scholars active today, it is Jens Bartelson who has done the most in terms of getting us to rethink our assumptions about the basic building blocks of our field. In a series of very significant books — A Genealogy of Sovereignty (1993), The Critique of the State (2001) and Sovereignty as Symbolic Form (2014)— as well as numerous articles, he has changed our understanding of both the concept of sovereignty and its conceptual history, with serious implications also for the history of ‘the state.’ His 2017 book War in International Thought has led the reader through the evolution of the thinking about war. And his most recent book Becoming International (2024), which is the subject of this review essay, joins Visions of World Community (2009) in getting us to rethink the very basic notion of ‘the international’ and how it came about

Connexin 43 is downregulated in advanced Parkinson’s disease in multiple brain regions which correlates with symptoms

Parkinson's disease (PD) is a neurodegenerative condition with the greatest increase in disability globally. Dysfunction of dopaminergic neurons is a well-known PD hallmark; however, changes in astrocytes also accompany PD progression. One aspect of astrocyte biology not yet investigated in PD is their network coupling. To assess this, we focussed on the major astrocytic gap junctional protein connexin 43 (Cx43, GJA1). A dataset of 20 post-mortem late-stage PD brain tissue samples from the cortex and basal ganglia alongside 20 age-matched control sets was collected, accompanied by clinical histories and data on -synuclein, tau, and amyloid-beta pathology. Protein levels and intracellular distribution of Cx43 and other key markers were measured. Computational re-analysis of open-source mRNA sequencing datasets from the striatum and midbrain complemented the original findings. Two novel observations were made: first, profound Cx43 loss in late-stage PD, and second, differential manifestation of this pathology in different brain areas, including those outside of the midbrain substantia nigra – the region that is most commonly used in PD research. Cx43 downregulation in specific regions correlated with non-motor symptoms of PD such as depression and sleep disturbance. Astrocytic tree simplification in the frontal cortex was further observed. In conclusion, astrocytic network decoupling through Cx43 downregulation in PD may contribute to astrocytic dysfunction and PD symptom development

Towards critical, anti-colonial and anti-racist education in national and global contexts

The fourth Sustainable Development Goal (SDG 4) of the United Nations (UN) 2030 Agenda aims to “ensure inclusive and equitable quality education and promote lifelong learning opportunities for all”. With over 122.6 million people worldwide forcibly displaced, and the number of refugees globally reaching 43.7 million by mid-2024, focusing on the importance of refugees accessing lifelong learning has become more urgent than ever. Despite this, refugees have been excluded from SDG-related national development plans, monitoring and reporting, raising questions about how the targets agreed in the Global Compact on Refugees and the SDGs are being implemented and met. Education, migration regulation and border regimes that reproduce injustices are fundamental elements of colonial education and have implications for lifelong learning. Education is often presented as crucial to the “integration” of migrants, including refugee people who have come to England. Nevertheless, the British government’s austerity policies, regarded by some as a form of racism, have underfunded the education system. This has made it more challenging for all learners from low-income families, and specifically refugee people, to access adequate education, amongst other rights. This article begins with a look at the assimilationist and apparent neutrality of approaches to education as sponsored by global and national commitments. The author then briefly discusses education as a practice of oppression, with colonial implications, including presenting perspectives from England and Brasil drawn from qualitative and mixed-methods doctoral and postdoctoral research. The article concludes by proposing approaches to enact education and lifelong learning as a practice of liberation rooted in critical, anti-racist and anti-colonial thinking and praxis

On the application of components manufactured with stereolithographic 3D printing in high vacuum systems

We explore the ultrahigh-vacuum (UHV) compatibility of Formlabs ‘Clear Resin’ via vat photopolymerisation (VPP). We report on a method for using VPP additive manufacturing, specifically Formlabs’ widely available stereolithographic (SLA) printing using their ‘Clear Resin’ material, to rapidly and cheaply prototype components for use in high-vacuum (HV) environments. We present pump down curves and residual gas analysis to demonstrate the primary vacuum contaminant from freshly printed SLA plastics is water with no evidence of polymers outgassing from the material and thus the vacuum performance can be controlled with simple treatments which do not involve surface sealing. An unbaked vacuum system containing SLA printed components achieved 1.9 × 10-8 mbar base pressure whilst retaining structural integrity and manufacturing accuracy. Outgassing rates in the HV test chamber and preliminary results in a UHV chamber indicate that our method can be extended to achieve ultrahigh-vacuum compatibility. We further report on the effect of atmospheric exposure to components and present evidence to suggest that water re-ad/absorption occurs exclusively on the surface, by showing that the bulk mass changes of the material is irreversible on the timescale investigated ( < 2 weeks)

Glucocorticoid treatment and new-onset hyperglycaemia and diabetes in people living with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

INTRODUCTION: In people living with chronic obstructive pulmonary disease (COPD), we aimed to estimate: (1) the prevalence of glucocorticoid-induced hyperglycaemia (GIH); (2) whether the prevalence of GIH varies by age, baseline diabetes status, treatment duration, ascertainment of glycaemia, definition of hyperglycaemia, study design and year of publication; and (3) the relative risk (RR) of new-onset hyperglycaemia in exposed vs non-exposed to systemic glucocorticoids. METHODS: We searched electronic databases until 9 November 2023 for randomised controlled trials and observational studies including adults diagnosed with COPD, with or without diabetes at baseline, using systemic glucocorticoids equivalent to prednisolone ≥5 mg/day for ≥3 days if exposed. Hyperglycaemia was defined as a blood glucose above a study-specific cut-off. We extracted data on study and participant characteristics, exposure and outcome. We performed random-effects meta-analysis to calculate pooled prevalence estimate of GIH. Prevalence was expressed as the proportion of people who developed hyperglycaemia among all exposed to systemic glucocorticoids during follow-up. We calculated RR of new-onset hyperglycaemia in exposed vs non-exposed to systemic glucocorticoids from eight studies. RESULTS: Of 25,806 citations, we included 18 studies comprising 3642 people of whom 3125 received systemic glucocorticoids and 1189 developed hyperglycaemia. Pooled prevalence of GIH was 38.6% (95%CI 29.9%-47.9%) with significant heterogeneity, I2 = 96% (p < 0.010), which was partially explained by differences in study design. Pooled RR = 2.39 (95%CI 1.51-3.78). Publication bias was present. CONCLUSION: The prevalence of GIH was 38.6%. Being treated with systemic glucocorticoids for COPD was associated with 2.4 times higher risk of new-onset hyperglycaemia versus no glucocorticoid treatment

Predicting incident dementia in community-dwelling older adults using primary and secondary care data from electronic health records.

Predicting risk of future dementia is essential for primary prevention strategies, particularly in the era of novel immunotherapies. However, few studies have developed population-level prediction models using existing routine healthcare data. In this longitudinal retrospective cohort study, we predicted incident dementia using primary and secondary care health records at 5, 10 and 13 years in 144 113 Scottish older adults who were dementia-free prior to 1st April 2009. Gradient-boosting (XGBoost) prediction models were trained on two feature subsets: data-driven (using all 171 extracted variables) and clinically supervised (22 curated variables). We used a random-stratified internal validation set to rank top predictors in each model, assessing performance stratified by age and socioeconomic deprivation. Predictions were stratified into 10 equally sized risk deciles and ranked by response rate. Over 13 years of follow-up, 11 143 (8%) patients developed dementia. The data-driven models achieved marginally better precision-recall area-under-the-curve scores of 0.18, 0.26 and 0.30 compared to clinically supervised models with scores of 0.17, 0.27 and 0.29 for incident dementia at 5, 10 and 13 years, respectively. The clinically supervised model achieved comparable specificity 0.88 [95% confidence interval (CI) 0.87-0.88] and sensitivity (0.55, 95% CI 0.53-0.57) to the data-driven model for prediction at 13 years. The most important model features were age, deprivation and frailty, measured by a modified electronic frailty index excluding known cognitive deficits. Model precision was consistent across socioeconomic deprivation quintiles but lower in younger-onset (<70 years) dementia cases. At 13 years, dementia was diagnosed in 32% of the population classified as highest risk with 40% of individuals in this group below the age of 80. Personalized estimates of future dementia risk from routinely collected healthcare data could influence risk factor modification and help to target brain imaging and novel immunotherapies in selected individuals with pre-symptomatic disease

Diversity, Equity and Inclusivity‐ Low and Middle Income countries and the Lancet commission

Background: Data from high‐income countries (HICs) suggest a decline in age‐specific incidence rates of dementia. However, this has happened primarily in HICs, with low‐ and middle‐ income countries (LMICs) facing two main challenges: a higher burden of risk factors and, in general, a faster ageing population. Most people with dementia live in LMICs, and this is set to increase, thus requiring urgent and robust action to prevent, treat and support people with dementia and their families. Methods: We, in the Lancet Commission, reviewed the most recent literature, and conducted a new metanalysis on worldwide dementia risk. We have calculated worldwide figures, although there may be variation in different ethnic and socioeconomic groups. Results: Dementia studies are overwhelmingly from HICs, and there is a tendency to recruit people of European origin with higher education and socioeconomic status, with few people from ethnic minority groups. The same applies in respect of worldwide clinical trials, including multicomponent interventions to reduce risk, biomarker research and pharmacological/non‐pharmacological interventions. Although most interventions are developed in HICs, culturally adapted interventions seem to be as effective in LMICs as in their original context, as long as the interventions’ core components are not compromised in the adaptation process. Conclusion: Policy interventions can improve dementia prevention, particularly in LMICs and in minority and lower level socio‐economic groups ‐ precisely the people who have the greatest burden of modifiable risk and are more likely to develop dementia. Dementia prevention efforts should be tailored to the needs of the different countries and different groups within countries. Trials and research databases should aim for sociodemographic diversity to reflect real life populations. Although evidence‐based interventions developed in HICs can be effective in LMICs, there is often a lack of healthcare infrastructure and resources to deliver them. Moreover, cultural differences can make them inappropriate or less effective. Interventions should be developed in partnership with local communities to ensure their appropriateness in respect of the culture, beliefs and practises which vary within and between countries

What does "sustainable seafood" mean to seafood system actors in Japan and Sweden?

"Sustainability" can mean different prioritisations of society, environment and economy to different people. As one of the largest globally traded food commodities, for seafood, these differences could have large implications. The study captures different understandings of "sustainable seafood" among 29 key actors along the seafood supply chain-government, NGOs, industry bodies, retailers and producers-using a novel cross-country application of Q method in Japan and Sweden. Sweden, known for its uptake of green consumption, contrasts with Japan's focus on alternative sustainability initiatives such as satoumi. Participants ranked 40 prepared statements on seafood sustainability revealing four distinct perspectives: Regulation-centric, Ecocentric, Industry-centric and Community-centric. There were clear country-based divisions, with only one perspective containing participants from both countries. Interactions and prioritisations of different dimensions of sustainability are also presented, through which we hypothesise areas of conflict and consensus. We stress the need to understand diverse perspectives when tackling global seafood sustainability challenges

Ultrasensitive Protein Aggregate Quantification Assays for Neurodegenerative Diseases on the Simoa Platform.

Nanoscale aggregates play a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. However, quantifying these aggregates in complex biological samples, such as biofluids and postmortem brain tissue, has been challenging due to their low concentration and small size, necessitating the development of methods with high sensitivity and specificity. Here, we have developed ultrasensitive assays utilizing the Quanterix Simoa platform to detect α-synuclein, β-amyloid and tau aggregates, including those with common posttranslational modifications such as truncation of α-synuclein and AT8 phosphorylation of tau aggregates. All assays had a detection limit in the low pM range. As a part of this work, we developed silica-nanoparticle calibrators, allowing for the quantification of all aggregates. These assays were validated for aggregate and target specificity through denaturation and cross-reactivity experiments. We then applied these assays to brain homogenate samples from Alzheimer's disease and control samples, demonstrating their applicability to postmortem tissue. Lastly, we explored the potential of these assays for blood-based diagnostics by detecting aggregates in serum samples from early Alzheimer's disease patients

Fulminate: Testing CN Separation-Logic Specifications in C

Separation logic has become an important tool for formally capturing and reasoning about the ownership patterns of imperative programs, originally for paper proof, and now the foundation for industrial static analyses and multiple proof tools. However, there has been very little work on program testing of separation-logic specifications in concrete execution. At first sight, separation-logic formulas are hard to evaluate in reasonable time, with their implicit quantification over heap splittings, and other explicit existentials. In this paper we observe that a restricted fragment of separation logic, adopted in the CN proof tool to enable predictable proof automation, also has a natural and readable computational interpretation, that makes it practically usable in runtime testing. We discuss various design issues and develop this as a C+CN source to C source translation, Fulminate. This adds checks – including ownership checks and ownership transfer – for C code annotated with CN pre- and post-conditions; we demonstrate this on nontrivial examples, including the allocator from a production hypervisor. We formalise our runtime ownership testing scheme, showing (and proving) how its reified ghost state correctly captures ownership passing, in a semantics for a small C-like language