Background: Acute Necrotizing Encephalopathy of Childhood (ANEC) is an illness characterized by rapidly progressive encephalopathy, typically associated with a precipitating viral illness such as influenza. It is diagnosed clinically and through neuroimaging showing symmetric multifocal lesions involving the deep grey matter, especially the thalamus. Morbidity and mortality in ANEC are high, so prompt recognition and treatment are key, but treatment protocols vary. We propose a management protocol based on a consensus approach and available evidence. Methods: A rapid literature review was conducted. Studies included were meta-analyses, case series, and expert consensus guidelines. Individual case reports were excluded. We identified interventions which have been used, and selected those with evidence or expert support for use in a protocol. The protocol was reviewed with stakeholders in pediatric neurology and PICU. Results: Reported treatments include high-dose steroids, IV immunoglobulins, tocilizumab, and plasmapheresis. The treatment with strongest evidence is high-dose steroids started within 24 hours of presentation. There is frequently reported use of IV immunoglobulins and plasmapheresis, and growing evidence to support use of tocilizumab (IL-6 blockade) within the first 48 hours. Conclusions: Overall, there is strong expert opinion that treatment should be initiated promptly. We present our centre’s protocol to expedite this treatment.

While it is vital to agree to a set of global objectives and targets to reduce plastic pollution as part of the Global Plastic Treaty, past negotiations have been troubled by differences in regional and national priorities and needs. To take these different priorities and needs into account, this letter proposes the adoption of an interdisciplinary source-to-sea approach. A source-to-sea approach emphasizes the connected nature between land-based sources of marine plastic pollution along the life cycle of plastic products on the one hand, and air, soil, and water cycles that determine marine plastic flows and associated sustainability risks on the other hand. It takes into account how we know more about the way in which production, use and plastic waste contribute to the pollution of rivers and seas in one location (e.g. in Europe), than we do for rivers and seas in other places (e.g. Africa). There are also regional and national differences in how much awareness exist about plastic pollution and how it is governed and regulated. These differences translate in different priorities and needs in terms of how to most efficiently and effectively reduce plastic pollution. The letter argues that these differences should be embraced and that an interdisciplinary source-to-sea approach can help to develop tailor-made regional and national targets and measures that in turn contribute to achieving the global ambitions of the Global Plastic Treaty. A key role is foreseen for existing governance institutions, such as river basin commissions and regional seas conventions (coordinated by UNEP Regional seas Programme), while the Global Plastic Treaty can become a platform for sharing of approaches, lessons and strategies between regions and countries so that over time, plastic pollution will be reduced worldwide.

Background: New neural antibodies are being identified each year and determining how to measure them and how to interpret test results is complex. In addition, screening with two methods is recommended for most antibodies, particularly paraneoplastic antibodies. We report the clinical validation and profile of a series of neural autoantibodies detected with a comprehensive testing algorithm. Methods: This is an ongoing study in which we are asking for the clinical correlation and final diagnosis of patients whose serum and/or CSF samples were tested at the BC Neuroimmunology Lab, Vancouver for neural autoantibodies. We performed immunofluorescence screening assay/IHC in rat brain sections in combination with confirmatory fixed or live Cell-Based assays and/or immunoblots. Results: We obtained clinical information from 219 samples (22 positive), Upon clinical inquiry, we obtained clinical information on 12 cases (five positive and seven negative). One Ttitin positive case was associated with anti-acetylcholine receptor antibody myasthenia and one Zic4 antibody was detected as a false positive by immunoblot but was negative by Rat Brain IHC. Conclusions: We have identified 10 percent seropositivity on 219 samples testing for Mosai-6 and full paraneoplastic testing. Further clinical validation studies are ongoing to evaluate the accuracy of our serological testing for neural antibodies.

Background: Drug-resistant epilepsy (DRE), defined by persistent seizures despite appropriate anti-seizure medication trials, affects about one-third of individuals with epilepsy. Deep brain stimulation (DBS) has emerged as a promising avenue for improved seizure control. This project reviews existing publications to better understand the neuromodulation parameters used in DBS, aiming to inform clinical decisions on optimizing treatment parameters in patients living with DRE. Methods: A comprehensive literature search of PubMed and Google Scholar was conducted using the keywords “DBS,” “epilepsy,” and “parameters.” Only original studies reporting specific stimulation parameters were included, with meta-analyses and review papers excluded. A weighted Pearson correlation, using study sample size as the weight, examined frequency, pulse width, seizure reduction, and responder rate. Results: So far, 28 studies (1997-2024) have been reviewed, encompassing a total of 1,054 patients, with study size ranging from 1-250 patients. Electrode targets included the hippocampus, ANT, amygdala, centromedian nucleus, and STN. DBS frequencies ranged from 60–333 Hz, and pulse widths from 40–450 µs. Pearson correlation results suggest moderate frequencies (130–145 Hz) and wider pulse widths (300–450 µs) correlate with better seizure reduction and higher responder rates. Conclusions: These results support a formal meta-analysis to further investigate neuromodulation parameters to improve outcomes for DRE patients.

Although much has been written on legislative reciprocity, rarely have scholars had an opportunity to leverage a randomly assigned asset to assess whether and how legislators reciprocate when their colleagues assist them. Using the lottery that allows Canadian Members of Parliament (MPs) to propose bills or motions, we examine whether MPs’ priority numbers affect their proclivity to second motions made by other MPs, which would be expected if MPs sought to build support for their own proposals by supporting proposals by others. Although MPs almost always make a proposal if their priority number allows them to do so, we find a weak relationship between MPs’ priority numbers and their probability of seconding others’ proposals. Moreover, when we look at successive parliaments, we see only faint indications that those who, by chance, won the right to propose in the previous session (and who therefore were eligible to attract seconds) are more likely to second others’ proposals in the current session. Although subject to a fair amount of statistical uncertainty that will gradually dissipate as future parliaments are examined, this pattern of evidence currently suggests that correlated seconding behavior among legislators is more the product of homophily than reciprocity.

Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.

Does the presence of two or more transborder minorities alter the logic of nation-building and affect minority securitization? This article goes beyond the triadic nexus framework commonly applied to minorities caught between their home- and kin-states, proposing a complex lens for analyzing states with multiple ethnic minorities. Titular political elites dealing with multiple minorities assign them to contradictory frames to manage the challenging reality of ethnic demography and regional security. By framing one minority as a “model minority” — trustworthy and law-abiding — and another as a “fifth column” — threatening and disruptive – they accomplish two aims: (1) maintain the dominant status of the titular nation by discrediting minority claims for institutional changes, and (2) legitimize the differential treatment of minorities. Ethnic minorities’ responses to these frames vary from relative acquiescence to violent conflict. I explore why the initially excluded Poles have been recently accommodated in Lithuania, why the marginalized Uzbeks became targets of repression in the Kyrgyz Republic, and why the relatively accommodated Russian speakers, former colonizers, became framed as a security threat in Lithuania but not in the Kyrgyz Republic after the Russian invasion of Ukraine. Understanding how strategic framing advances nation-building offers generalizable insights on (de)securitization of ethnicity.

Background: Over 1.3 million people in North America participate in tackle football annually. Football players experience a disproportionately higher risk for repetitive non-concussive impacts (NCIs) compared to other high-contact sports athletes. Quantifying how this exposure influences a player’s cognitive function is imperative. While NCIs share the same mechanism as concussions, they do not elicit immediate symptoms. Methods: This study tracked impact exposure in 13 male Queen’s Varsity Football players using six-axis mouthguard accelerometers throughout the season. Electroencephalography (EEG) recordings were conducted at two time points (pre-season and post-season) to measure event-related potentials (ERPs), evaluating auditory sensation, basic attention, and cognitive processing. Results: Analysis of pre- and post-season EEGs revealed group differences in N100 and N400 wave amplitudes but found no correlation between impact exposure metrics (including varying magnitudes, frequencies, and linear and angular accelerations) and deficits in attention or cognitive processing. Conclusions: These findings suggest that a single season of football-related NCIs may not be sufficient to produce detectable changes in cognitive function as measured through ERPs, despite the variation in impact exposure. Further longitudinal studies spanning multiple seasons and additional neurophysiological measures may be necessary to fully understand the cumulative effects of NCIs on cognitive function in football players.

Background: Molecular characterization of spatially heterogeneous tumors, such as primary brain tumors, requires precise, contamination-free tissue collection. This study develops a novel biopsy instrument enabling efficient, spatially registered tissue collection across tumors and surgical cavities, advancing personalized tumor characterization and treatment. Methods: Iterative modeling and 3D printing were used to develop prototypes, which underwent proof-of-concept and phantom testing. Final device evaluation compared the novel capsule biopsy tool to Yasargil tumor grasping forceps, with six neurosurgeons and six students conducting tests on porcine brain. Additionally, intraoperative samples were collected, with spatial coordinates recorded on preoperative scans. Results: The design features a capsule that attaches to the end of a Frazier suction. When suction is applied, an internal piston secures the sample, which can later be released before or after tissue fixation. The capsule method reduced variability in sample weight and collection time compared to Yasargil forceps, maintaining tissue integrity without contamination or instrument failure. Notably, students demonstrated proficiency comparable to experienced surgeons, highlighting the tool’s ease of use. Conclusions: This low-cost, optically tracked biopsy tool provides an efficient, reliable method for spatially precise tissue collection, meeting the demands of precision medicine and translational research.

Reparations for African Americans reflect both material concerns aimed at eliminating the Black–White racial wealth gap and symbolic political aspirations, including the end of structural racism. But do material or symbolic considerations drive policy evaluations across racial and partisan divides? What knowledge and experiences undergird processes through which individuals weigh the symbolic importance of a policy against its actual benefits? Leveraging a set of forty-one in-depth interviews with Black and White residents of Evanston, Illinois—the first municipality in the United States to approve a publicly-funded reparations-related ordinance—we highlight a mechanism through which individuals develop their opinions about reparations: political socialization. Black interviewees linked their understanding of reparations to robust financial compensation while White Democrats viewed their support for Evanston’s policy as symbolic of their longstanding, affective commitments to racial equality. Drawing from these observations, we present a framework highlighting policy attributes that frame how different constituencies respond to reparations-related policies. We test this framework using a conjoint experiment about reparations policies fielded in the 2022 Cooperative Election Study. We find Americans—especially White Republicans—possess less familiarity about reparations and remain strongly opposed to these policies, regardless of the form they take. While White Democrats are more familiar with reparations and more supportive of policies mirroring Evanston’s, Black Americans—those who are most familiar with reparations—support direct cash payments regardless of their political identification.

Background: This study evaluates the utility of CT angiography (CTA) and the Expanded Denver Criteria (EDC) in detecting blunt cerebrovascular injuries (BCVI) in blunt cervical trauma, assaults, and strangulation. Methods: A retrospective review of 748 patients undergoing CTA for blunt cervical trauma, assaults, and strangulation (2013–2023) was conducted. After exclusions, 344 CTA reports were analyzed. Inclusion criteria: patients ≥18 years with complete medical records who underwent CTA for trauma evaluation. Exclusions: penetrating injuries, preexisting cerebrovascular abnormalities, incomplete records, or CTA not performed. Results: BCVI was identified in 38/344 cases (11%), with 55% classified as Grade I (Biffl). Posterior circulation (71%) and internal carotid arteries (36.8%) were most affected. Eight BCVI cases (21%) did not meet EDC; MVCs accounted for seven. MVCs (68%) and falls (29%) were the leading causes, while no BCVIs were observed in assaults or strangulations. Conclusions: MVCs and high-impact falls pose the highest BCVI risk, warranting CTA beyond EDC indications. In contrast, CTA may be less necessary for assaults and strangulations. Further studies across trauma centers are needed to confirm these findings.

Background: Glioblastoma (GB) is the most malignant primary brain tumor. Isolated restricted diffusion (IRD) is restricted diffusion outside the confines of enhancing tumor with no corresponding enhancement on post contrast study. The aim of our study was to prospectively assess the incidence of IRD in GB patients, determine how often these foci proceed to contrast enhancement on follow up, and analyze the survival pattern. Methods: In a prospective pilot cohort study, consecutive adult patients with GB on initial MRI of brain, were included and screened for IRD. All images were independently analyzed by two experienced radiologists. The survival pattern of patients with IRD was assessed with Cox-regression and Kaplan-Meier curve analysis. Results: Of the 52 patients (median age- 63 years; male-63.5%), 21% (11 of 52) exhibited IRD. Inter-rater agreement on the diagnosis of IRD foci was fair (kappa=0.29). Seven (64%) showed enhancement in the IRD focus. The Kaplan Meier analysis revealed a significant decrease (p=0.035) in the survival was observed among patients with IRD focus. Conclusions: IRD focus was seen in 21% of patients with GB, with 64% of these demonstrating enhancement at the IRD focus on follow up imaging. A shorter survival was associated with IRD foci.

A dimer model is a quiver with faces embedded in a surface. We define and investigate notions of consistency for dimer models on general surfaces with boundary which restrict to well-studied consistency conditions in the disk and torus case. We define weak consistency in terms of the associated dimer algebra and show that it is equivalent to the absence of bad configurations on the strand diagram. In the disk and torus case, weakly consistent models are nondegenerate, meaning that every arrow is contained in a perfect matching; this is not true for general surfaces. Strong consistency is defined to require weak consistency as well as nondegeneracy. We prove that the completed as well as the noncompleted dimer algebra of a strongly consistent dimer model are bimodule internally 3-Calabi-Yau with respect to their boundary idempotents. As a consequence, the Gorenstein-projective module category of the completed boundary algebra of suitable dimer models categorifies the cluster algebra given by their underlying quiver. We provide additional consequences of weak and strong consistency, including that one may reduce a strongly consistent dimer model by removing digons and that consistency behaves well under taking dimer submodels.

Impaired glycaemic control is a major risk factor for developing type 2 diabetes (T2D), a worldwide health epidemic intrinsically linked to diet and obesity. Whey proteins (WP) are increasingly popular supplements that are a rich source of branched-chain amino acids (BCAA), essential for muscle protein synthesis and metabolic regulation. In humans, fasting plasma concentrations of BCAA are maintained around 350 µM but become chronically elevated by 10–25% in persons with T2D. Little is known about whether BCAA from WP impacts circulating BCAA concentrations and contributes to this phenomenon. This narrative review used a systematic search approach with relevant keywords to identify evidence from randomised controlled trials in normoglycaemic humans and those with insulin resistance or T2D, on the effects of WP intake on plasma BCAA and glycaemic control. This review is, to the authors’ knowledge, the first to specifically examine the effects of WP intake on plasma BCAA concentrations in relation to glycaemic control. Whilst the majority of acute studies identified (n = 6) reported that WP consumption between 10 and 50 g significantly elevates postprandial BCAA and insulin responses (as evidenced by peak concentration and/or area under the curve), evidence from chronic studies (n = 3) report inconsistent findings on the impact of 9–51 g of WP/d on fasting BCAA and glycaemic control (for example, fasting glucose and insulin, insulin clearance). Findings from this literature review highlight the need for further studies that investigate the relationship between WP consumption with BCAA and glycaemic control, and to determine underlying mechanisms of action.

Background: Fluorescence-guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) is a well-established tool for improving tumor visualization in glioma surgery. However, its applications in non-glioma pathologies remain underexplored and require further investigation. Methods: A retrospective review of patients who underwent FGS with 5-ALA between January 2022 and September 2024 was conducted to assess its utility in non-glioma tumors. Results: Among 232 FGS procedures, 13 (5.6%) involved non-glioma pathologies. We categorized our patients into three different levels: high, moderate, and no response based on intra-operative 5-ALA fluorescence visualization. Our patients showed a high 5-ALA fluorescence in 10 cases (77%), mainly in the following tumors: choroid plexus papilloma, atypical teratoid rhabdoid tumor, metastatic adenocarcinoma as well as atypical meningiomas. Moderate 5-ALA fluorescence was seen in 2 cases (15%). While no 5-ALA fluorescence was seen in one case of CNS lymphoma. 90% of procedures with high response had total resection. Conclusions: Fluorescence-guided surgery (FGS) using 5-ALA has demonstrated effectiveness in enhancing tumor visualization beyond gliomas. This retrospective review highlights the potential applications of 5-ALA in various non-glioma pathologies. These findings emphasize the need for further research to refine the use of 5-ALA FGS in diverse pathologies, optimize patient selection, and expand its utility in neurosurgical oncology.

Background: While developing a differentiation therapy for Sonic Hedgehog Medulloblastoma (MB), we discovered a potential paradoxical feedback cycle between Ezh2, a protein that temporarily keeps differentiation genes silenced via trimethylating H3K27, and Cyclin D1, a protein that regulates cell cycle entry. Methods: We quantified H3K27me3 in P7 purified cerebral GNPs using chromatin immunoprecipitation sequencing and correlated it with gene expression via RNA sequencing (RNAseq). To assess transcriptional effects of Ezh2 loss, we purified P7 GNPs from Math1-Cre, Ezh2-flox knockout mice. MB cells were cultured in suspension spheres and imaged using the ImageXpress Micro XLS system, with nuclei segmented based on DAPI staining. Results: Cyclin D1 ranked among the top 7.37% of expressed genes but was heavily marked by the repressive histone mark H3K27me3 (top 5.5%) in GNPs. Ezh2 overexpression increased G0-arrested MB cells 2.7-fold, while, in GNPs, RNAseq showed significant Cyclin D1 upregulation in Ezh2 knockout mice (Log2FC: 1.301). Cyclin D1 regulates the pRb/E2F1 complex, and we observe that Ezh2 expression depends on pRb/E2F1 complex abundance, forming a feedback loop. Notably, combining the Hedgehog inhibitor Vismodegib with an Ezh2 inhibitor rescued MB cells from Vismodegib-induced death. Conclusions: Our study introduces a model that promotes GNP differentiation, leading tumor cells to differentiate into neurons.