This paper considers two commuting smooth transformations on a Banach space and proves the sub-additivity of the measure theoretic entropies under mild conditions. Furthermore, some additional conditions are given for the equality of the entropies. This extends Hu’s work [Some ergodic properties of commuting diffeomorphisms. Ergod. Th. & Dynam. Sys. 13(1) (1993), 73–100] about commuting diffeomorphisms in a finite dimensional space to the case of systems on an infinite dimensional Banach space.

Background: In Canada, individuals with intellectual disabilities (ID) make up approximately 25% of the epilepsy population. Despite making up only a small portion, adult hospitalization data in Canada shows that individuals with ID are significantly more likely to be seen in the ED, be hospitalized, and to die as a result of epilepsy and epilepsy complications, than individuals with typical cognitive development. Data looking at ED visits in adolescents with epilepsy and varying cognitive abilities is extremely limited. Methods: To address this, a retrospective chart review of 122 adolescents (42 MID and 80 typical cognitive development) with epilepsy between the ages of 14 and 18 was done. Results: Results showed that adolescents with typical cognitive development had significantly more ED visits (p=.006), and seizure related ED visits (p= .008) than adolescents with MID. Despite the reasons for ED visits not significantly differing between the two groups, adolescents with MID had significantly longer ED visits (p=.023). Finally, when looking exclusively at the MID group, results showed that females were significantly more likely to be seen at the ED than males (p=.001). Conclusions: Results suggest that ED visit frequencies differ among adults and adolescents with ID, potentially suggesting the presence of unique protective factors for adolescents.

Background: Advanced parkinsonian syndromes represent a growing challenge for healthcare systems as their care needs are complex and costly. Current care models often lack integration of specialized neurology and palliative care, leading to suboptimal outcomes. The Advanced Care Team for Parkinson’s program (ACT-PD) addresses this gap by enhancing care quality and reducing costs. This study evaluates the cost-effectiveness of ACT-PD interventions compared to standard care (SC). Methods: A retrospective analysis compared 27 deceased ACT-PD patients (2022–2024) with 1,439 deceased SC patients (2011–2017). It assessed healthcare utilization, place of death, and patient Quality-Adjusted Life Years (QALYs). Healthcare utilization measures included hospitalizations, Intensive Care Unit (ICU) admissions, emergency department (ED) visits, and palliative care consultations. The analysis incorporated the incremental cost-effectiveness ratio (ICER) using Calgary Zone cost data from 2021–2022. Results: ACT-PD patients experienced fewer hospital deaths (33.33% vs. 45.90%) and more deaths at home (22.22% vs. 7.90%). They also had greater neurology (48.00% vs. 37.20%) and palliative care engagement (36.00% vs. 17.40%). ACT-PD avoided ICU admissions, saving $2.56 million annually, with total cost savings of $2.66 million. The ICER was $1,459 per QALY gained. Conclusions: Multidisciplinary palliative care interventions provided by ACT-PD are highly cost-effective, improving care quality while reducing healthcare costs.

The frequency responses of circulation control and separation control using mini-spoilers for loads attenuation on plunging swept and unswept wings were compared in a water tunnel study. At the pre-stall angle-of-attack, the effectiveness of the spoilers significantly diminishes with increasing reduced frequency of the plunging motion. For the leading-edge spoiler, this happens because the roll-up of the vorticity promotes flow reattachment and reduces the effectiveness of loads attenuation. For the trailing-edge spoiler, the effectiveness of lift attenuation also decreases with increasing reduced frequency, due to the shedding of leading-edge vortices and immersion of the trailing-edge spoiler in the separated flow. The decay of the frequency response for both types of spoilers is similar, implying that it is dictated by the flow separation near the leading edge of the wing in both cases. With increasing sweep angle of the wings, the spoilers’ effectiveness decreases significantly in comparison to the unswept wing. Strong spanwise flow develops for the leading-edge spoiler, which sheds a streamwise vortex, with the same direction of rotation as the wing-tip trailing vortex. This causes partial reattachment of the flow and reduction of the separation area behind the spoiler. With increasing reduced frequency, strong leading-edge vortices dominate the flow over the wing. The leading-edge vortices generate additional vortex lift and also cause the trailing-edge spoiler to be immersed in the massively separated flows. Both factors reduce the effectiveness of the spoilers.

Background: Tuberous Sclerosis Complex (TSC) is a genetic condition marked by multisystem benign tumours. mTOR inhibitor (mTORi) therapy is indicated for subependymal giant cell astrocytomas (SEGA), renal angiomyolipomas (AML), and drug-resistant epilepsy. This study aimed to evaluate the efficacy and safety of mTORi in our paediatric TSC cohort. Methods: Data on patient demographics, clinical outcomes, and adverse events (AEs) were obtained from SickKids’ prospective observational TSC Database (n=107). Results: 19 children (median age at diagnosis 0.6 years, range 0-8.3; F:M 10:9) received mTORi. Indications were SEGA (n=6), AML (n=4), seizures (n=4), prophylactic (n=2), AML/SEGA (n=1), seizures/AML (n=1), and seizures/SEGA (n=1). Median age at mTORi initiation was 8.4 years (range 2.1-15.4). 68.4% (n=13/19) received sirolimus and 31.6% (n=6/19) received everolimus. 24 months post-mTORi initiation, 50% showed stable SEGA (n=4/8), 50% reduced SEGA (n=4/8), 66.7% stable AML (n=8/12), 25% reduced AML (n=3/12), and 8.3% larger AML (n=1/12). Variability in reporting seizure frequency rendered mTORi effects on epilepsy inconclusive. mTORi was overall well tolerated, yet 100% (n=19/19) reported AEs, majority Grade 1-2. Conclusions: This study describes the efficacy and tolerability of mTORi in a Canadian paediatric TSC cohort, which demonstrates beneficial effects on SEGA and AML, with mild to moderate AEs reported.

Background: Mesial temporal lobe epilepsy (mTLE) is a heterogenous condition with variable post-surgical outcomes. Combining high resolution magnetic resonance imaging (MRI), stereoelectroencephalography (SEEG) and histology may establish different subtypes of mTLE. Methods: Retrospective analysis of patients with mTLE with 1) SEEG Patterns 2) MRI 3) Post temporal lobectomy tissue analysis 4) Engel Classification. HippUnfold method was used to segment hippocampus on MRI. Results: Of 109 patients investigated with SEEG, 11 patients were analyzed so far. Low voltage fast activity was seen in 215 seizures, low-frequency periodic spikes in 21, sharp activity at <13 Hz in 58, rhythmic spike sharp wave activity in 86, and other types were less frequent. MRI revealed unilateral mesial temporal sclerosis (MTS) in 6 (54.55%), bilateral MTS in 2 (18.18%), and was normal in 3 (27.27%) patients. Histopathology showed ILAE grade I in 3 (37.5 %), II in 4 (50 %), IV in 1 (12.5%) patient. 63.63% had Engel Class I at 6 months. HippUnfold analysis and SEEG electrode coregistration was done in one patient and will be attempted in the rest. Conclusions: Our study highlights a strong correlation between SEEG findings and histological analysis in mTLE. A multidimensional classification will help predict long term outcomes.

Background: We’ve adopted a novel approach that combines cellular barcoding with CRISPR/Cas-9 technology and single-cell RNA sequencing known as continuous lineage tracing to track the development, treatment and inevitable recurrence of glioblastoma. Methods: Patient derived glioma initiating cell lines were engineered with expressed DNA barcodes with CRISPR/Cas-9 targets and engrafted into NOD scid-mice. Clonal and relationships are surmised through identification of expressed barcodes, and cells were characterized by their transcriptional profiles. Phylogenetic lineage trees are created using lineage reconstructive algorithms to define cell fitness and expansion. Results: Our work has revealed a significant amount of intra-clonal cell state heterogeneity, suggesting that tumour cells engage in phenotype switching prior to therapeutic intervention. Phylogenetic lineage trees allowed us to define a gene signature of cell fitness. GBMs exist along a transcriptional gradient between undifferentiated but “high-fit” cells and terminally differentiated, “low-fit” cells, lending further evidence that these tumours consist of pools of cells that are capable of recapitulating the tumour microenvironment after treatment. Conclusions: We have successfully engineered a set of glioma initiating tumours with a novel lineage tracing technique, creating a powerful tool for real-time tracing of tumour growth through the analysis of highly detailed singe-cell RNA sequencing data with associated clonal and phylogenetic relationships.

Background: Ontario and other Canadian provinces fund multi-gene sequencing panels as the initial testing approach for patients with epilepsy. However, genetic testing guidelines issued by the US-based National Society for Genetic Counselors and endorsed by the American Epilepsy Society recommend exome as a first-line test. We explored the theoretical improvements in diagnostic yield when selecting exome over provincially-funded panels (PFPs). Methods: Our comparative analysis used a list of 768 diagnostic genes and 4474 diagnostic variants identified in diagnostic exome cases involving clinical indications of seizure. We compared these lists to the genes included in two PFPs (190 genes and 474 genes) to see which exome-identified genes and variants would have been captured by the PFPs. Results: Most exome-identified diagnostic genes may have been missed by the PFPs (82% and 65% for the 190 and 474-gene PFPs), and close to half of the exome-identified diagnostic variants (62% and 43% for the 190 and 474-gene PFPs) may have been missed. Conclusions: Exome-based testing captures a broader range of diagnostic genes and more diagnostic variants than PFPs. The adoption of exome over panels as a first-line test may lead to improved diagnostic rates and permit earlier treatment for individuals with seizures.

Background: We aim to assess the resting state functional connectivity (RSFC) and reactivity with functional near-infrared spectroscopy (fNIRS) in patients with acute stroke compared to age, sex and comorbidity-matched subjects. Methods: Patients with acute anterior circulation stroke syndrome localizing to the right (RH) or left hemisphere (LH) were enrolled. RSFC was assessed using group-level seed-based (Primary Motor cortex,PMC) correlation analysis. Finger-tapping-associated relative oxygen Hemoglobin (ΔHbO) changes were analyzed with generalized linear model regression. Results: 127 participants (RH stroke, 51; LH stroke, 43; control, 33) enrolled at a median of 21 (15,29) hours after symptom onset. Compared to the control group, the RSFC with the affected PMC (LH stroke) was reduced over the affected somatosensory cortex (SSC) in the minor ischemic stroke (IS) (r = -0.14 (-0.3,-0.01)), minor intracerebral hemorrhage (ICH) (-0.48 (-0.78,-0.18)) and major ICH groups (-0.2 (-0.4,-0.01). In the FT task compared to the control groups in LH stroke, ΔHbO was increased over the affected SSC in minor IS (β11.2(1.9,20.5)) and major ICH group (β11.7 (1.4,22.1)). In the FT task in RH stroke, ΔHbO was increased over the unaffected PMC in minor IS (β12.1(2.3,21.8)), major IS (β14.9 (0.3,29.5)), minor ICH (β25.7 (10.1,41.2)) and major ICH (β13.4 (1.1,25.6). Conclusions: Motor cortex dysconnectivity may be worse over the LH stroke. In RH stroke, there is early compensatory increased neuronal activity over the unaffected PMC. These results suggest differential acute remodelling in RH and LH strokes.

Background: Routine electroencephalography (EEG) provides excellent temporal resolution for evaluation of focal epilepsy, but lacks spatial resolution. High-density-EEG (HDEEG)-based source-localization significantly enhances spatial resolution, but requires greater standardization. We systematically review HDEEG systems, methods, and metrics utilized for evaluating focal epilepsy. Methods: A systematic search was conducted in PubMed using PRISMA guidelines with keywords “HDEEG” or “high-density EEG”, “source localization and “focal epilepsy”. Inclusion criteria: studies from the last 20 years, human subjects with focal epilepsy, sample size ≥ 10 and HDEEG with source localization methods clearly described. Results: 37 of 65 studies fulfilled inclusion criteria, with most reporting N<50. Most studies (14) used a 256-electrode HDEEG setup; 10 used 128-electrode configurations, and 6 used 76–83 electrodes. EEG source localization most commonly used Cartool (N=12) and Curry (N=5) softwares. Standard MRIs were used in 25 studies, and customized MRIs in 12. Metrics like clustering coefficient were reported to represent dipole distribution (10 studies); while functional connectivity analysis was reported in 7 studies. Conclusions: Variations in software choice, metrics for dipole distribution assessment, and MRI integration are evident from the current literature. Clustering methods and functional connectivity metrics are most commonly employed to represent dipole distribution, reflecting their increasing utility in understanding brain networks.

Background: In generalized myasthenia gravis (gMG), there remains an unmet need for treatments providing meaningful symptom control. Methods: Mean changes in MG-ADL were compared between nipocalimab + standard-of-care (SoC) and placebo+SoC. The proportion of patients achieving: Minimal Symptom Expression (MSE), MG-ADL score 0/1, time with MSE, sustained within person meaningful change (WPMC) starting from Week 4, and time spent with WPMC were compared. Results: Nipocalimab+SoC demonstrated significant improvement in MG-ADL compared to placebo+SOC, LS-mean-change[SE] -4.7[0.329] vs -3.25[0.335]; Difference in means[SE]=-1.45 [0.470], p=0.002. The mean difference favoured nipocalimab+SoC, and was significant as early as week 1: LS-mean-change[SE]: -2.72[2.979] vs -1.77[2.426]; Difference in means[SE] -0.82[0.410], p=0.046. Nipocalimab+SoC patients were three times more likely to achieve MSE at any point during the study vs placebo; Odds Ratio[95% CI]: 3.0[1.3, 6.8]; 31.2% vs. 13.2%. For the 25 patients reaching MSE, the time sustaining MSE [percent time with MSE] was 101.5 days, (60.4%, nipocalimab+SOC) vs 55 days, (32.7%, placebo+SOC). Similarly, the proportion of patients with sustained WPMC favored nipocalimab+SOC, 55.8% vs 26.3%, placebo+SOC, p<0.001. The median percent time spent with WPMC was 84.5%, nipocalimab+SOC vs 39.9%, placebo+SOC, p=0.007. Conclusions: Based on MG-ADL data from Phase 3, nipocalimab an FcRn blocker, demonstrated rapid, substantial, and sustained symptom control.

Background: Amyotrophic Lateral Sclerosis (ALS) leads to progressive functional decline and reduced survival. Identifying clinical predictors like ALSFRS-R and FVC is essential for prognosis and disease management. Understanding progression profiles based on diagnostic characteristics supports clinical trial design and assessment of treatment response. This study evaluates disease progression and survival predictors in ALS patients from the CNDR. Methods: 1565 ALS patients in the CNDR were analyzed to assess baseline ALSFRS-R, FVC, time from symptom onset to diagnosis, and their association with disease progression and survival. Results: At diagnosis, ALSFRS-R was 44.7 (SD = 5.46), with 72.3% scoring ≥44. Mean FVC was 84.2% (SD = 23.3), with 78.3% of patients having FVC ≥65%. ALSFRS-R declined at 1.06 points/month (SD = 1.33), with faster progression in patients diagnosed within 24 months (1.61 points/month). Patients with ALSFRS-R ≥44 had a median survival of 41.8 months, compared to 30.9 months for those <44 (p < 0.001). Similarly, FVC ≥65% was associated with longer survival (35.4 vs. 29.5 months, p = 0.002). Conclusions: ALSFRS-R and FVC at diagnosis predict survival and inform clinical decision-making. These findings highlight the importance of early diagnosis and targeted interventions to slow disease progression and improve patient outcomes.

Background: Plasma pTau217 is a robust biomarker for the diagnosis of Alzheimer’s disease (AD). However, most pTau217 assays are not widely available for clinical testing. We assessed the performance of two commercially available plasma pTau217 immunoassays in a clinical diagnostic laboratory for AD diagnosis. Methods: 219 plasma samples from healthy controls with negative amyloid PET, 115 plasma samples from pathology-confirmed and 263 samples with confirmed amyloid PET were selected. Plasma pTau217 levels were measured using the ALZpath pTau217 assay on the Quanterix HD-X Simoa platform and the Lumipulse pTau217 assay on the Lumipulse G1200 platform at and BC Neuroimmunology Lab and Neurocode USA. Results: For the ALZpath assay, the coefficients were 10.4%, 10.4%, and 9.9%, and for the Fujirebio assay, were 12.1%, 12.2%, and 5.3%, respectively. Sample stability and interference were similar between the two assays, although moderate heterophilic antibody interference and reduced frozen sample stability at -20˚C were observed for the Fujirebio assay. Both assays demonstrated similar clinical performance and differentiated individuals with AD (ALZpath AUC = 0.94; Fujirebio AUC = 0.90). Conclusions: The performance of the two pTau 217 assays was comparable. The clinical separation between the healthy controls and those with Amyloid pathology was nearly complete for both assays.

Background: Treatment of aneurysmal subarachnoid hemorrhage (aSAH) in a high-volume center by experienced cerebrovascular and neuroendovascular surgeons improves outcomes. We studied whether rural aSAH patients experience treatment delays in British Columbia. Methods: Vancouver Ruptured Aneurysm Database (VRAD) started in 2023 to prospectively capture consecutive aSAH patients at Vancouver General Hospital (VGH), an academic neurosurgical hospital with comprehensive stroke center capabilities. We included patients ≥18 years-old, presenting ≤72h post-ictus and excluded untreated aneurysms and patients not residing in British Columbia. Patients were classified as rural or urban using the provincial government categorization of rurality. Results: We included 84 patients, 65.5% urban and 34.5% rural, with mean age 57.7 years (SD: 15.6) and 64.3% female. Aneurysm treatment consisted of 75% microsurgical clipping and 25% endovascular techniques. Median time from ictus to VGH was 5.9h [IQR: 2.6-16.6] urban and 13.2h [IQR: 8.3-27.8] rural, p=0.001. Median transfer time was 4.7h [IQR: 2.5-8.8] urban and 11.9h [IQR: 6.7-13.5] rural, p=0.006. Ictus to treatment time was 5.9h longer for rural patients, p=0.077. Conclusions: Rural aSAH patients in British Columbia take 7.3 hours longer to reach a neurosurgical center capable of comprehensive aneurysm treatment compared to urban patients. Improved inter-hospital transfer systems may reduce geographic disparities for aSAH in British Columbia.

Background: Brain-specific glial fibrillary acidic protein (GFAP) can discriminate stroke type [ischemic stroke (AIS), intracerebral hemorrhage (ICH), stroke mimics (SM)]. Novel point-of-care technology (GFAP levels <15 minutes) is a promising diagnostic tool. We aim to evaluate the feasibility of rapid GFAP analysis in acute stroke. Methods: Exploratory analysis of an ongoing prospective study of suspected undifferentiated stroke <24h from onset. Rapid plasma GFAP levels (pg/mL) are measured at hospital arrival using the i-STAT Alinity® instrument and commercially-available cartridges. Study endpoints include quantitative GFAP levels according to final diagnosis and time from stroke onset. Results: Among 200 patients (mean(±SD) 70.7±15.5 years, 44.5% female, median (IQR) NIHSS 9(4-19), diagnosis was AIS (n=132 (59 large-vessel occlusion), ICH (n=17), and SM (n=51). Median time from hospital arrival to GFAP result was 56.0 (47.0-69.5) minutes. Median rapid GFAP levels were highest in ICH (878.0 (70.5-3,906.5) pg/mL) compared to AIS (49.5 (29.0-95)pg/mL) and SM (29(29-64)pg/mL), p=0.001. Median GFAP was higher in AIS-known onset >4.5h (n=9) (110.0 (44.0-216.0) pg/mL) compared to AIS<4.5h (40.5 (29.0-68.8) pg/mL) (n=72), (p=0.047), while AIS-unknown onset (n=51) (68.0 (29.0-108.5) pg/mL) fell between these two groups, likely reflecting the subgroup’s heterogeneity. Conclusions: Preliminary findings suggest that rapid GFAP analysis is feasible in acute stroke and may inform treatment decisions.

The family of relevant logics can be faceted by a hierarchy of increasingly fine-grained variable sharing properties—requiring that in valid entailments $A\to B$, some atom must appear in both A and B with some additional condition (e.g., with the same sign or nested within the same number of conditionals). In this paper, we consider an incredibly strong variable sharing property of lericone relevance that takes into account the path of negations and conditionals in which an atom appears in the parse trees of the antecedent and consequent. We show that this property of lericone relevance holds of the relevant logic $\mathbf {BM}$ (and that a related property of faithful lericone relevance holds of $\mathbf {B}$) and characterize the largest fragments of classical logic with these properties. Along the way, we consider the consequences for lericone relevance for the theory of subject-matter, for Logan’s notion of hyperformalism, and for the very definition of a relevant logic itself.

In previous publications, it was shown that finite non-deterministic matrices are quite powerful in providing semantics for a large class of normal and non-normal modal logics. However, some modal logics, such as those whose axiom systems contained the Löb axiom or the McKinsey formula, were not analyzed via non-deterministic semantics. Furthermore, other modal rules than the rule of necessitation were not yet characterized in the framework.

In this paper, we will overcome this shortcoming and present a novel approach for constructing semantics for normal and non-normal modal logics that is based on restricted non-deterministic matrices. This approach not only offers a uniform semantical framework for modal logics, while keeping the interpretation of the involved modal operators the same, and thus making different systems of modal logic comparable. It might also lead to a new understanding of the concept of modality.