In the past decade, researchers have been increasingly interested in understanding the process of language learning, in addition to the effect of instructional interventions on L2 performance gains (i.e., learning products). One goal of such investigations is to reveal the interplay between learning conditions, processes, and outcomes where, for example, certain conditions can promote attention to the learning targets, which in turn facilitates learning. However, the statistical modeling approach taken often does not align with the conceptualization of the complex relationships between these variables. Thus, in this paper, we introduce mediation analysis to SLA research. We offer a step-by-step, contextualized tutorial on the practical application of mediation analysis in three different research scenarios, each addressing a different research design using either simulated or open-source datasets. Our overall goal is to promote the use of statistical techniques that are consistent with the theorization of language learning processes as mediators.

Random-effects meta-analyses with only a few studies often face challenges in accurately estimating between-study heterogeneity, leading to biased effect estimates and confidence intervals with poor coverage. This issue is especially the case when dealing with rare diseases. To address this problem for normally distributed outcomes, two new approaches have been proposed to provide confidence limits of the global mean: one based on fiducial inference, and the other involving two modifications of the signed log-likelihood ratio test statistic in order to have improved performance with small numbers of studies. The performance of the proposed methods was evaluated numerically and compared with the Hartung–Knapp–Sidik–Jonkman approach and its modification to handle small numbers of studies. The simulation results indicated that the proposed methods achieved coverage probabilities closer to the nominal level and produced shorter confidence intervals compared to those based on existing methods. Two real examples are used to illustrate the proposed methods.

Background: Meningiomas are the most common intracranial tumors. Radiotherapy (RT) serves as an adjunct following surgical resection; however, response varies. RTOG-0539 is a prospective, phase 2, trial that stratified patients risk groups based on clinical and pathological criteria, providing key benchmarks for RT outcomes. This is the first study that aims to characterize the molecular landscape of an RT clinical trial in meningiomas. Methods: Tissue from 100 patients was analyzed using DNA methylation, RNA sequencing, and whole-exome sequencing. Copy number variations and mutational profiles were assessed to determine associations with meningioma aggressiveness. Tumors were molecularly classified and pathway analyses were conducted to identify biological processes associated with RT response. Results: High-risk meningiomas exhibited cell cycle dysregulation and hypermetabolic pathway upregulation. 1p loss and 1q gain were more frequent in aggressive meningiomas, and NF2 and non-NF2 mutations co-occurred in some high-risk tumors. Molecular findings led to the reclassification of several cases, highlighting the limitations of histopathologic grading alone. Conclusions: This is the first study to comprehensively characterize the molecular landscape of any RT trial in meningioma, integrating multi-omic data to refine treatment stratification. Findings align with ongoing genomically driven meningioma clinical trials and underscore the need for prospective tissue banking to enhance biomarker-driven treatment strategies.

Background: Recent research has demonstrated that DBS sites in Alzheimer’s (AD) and Parkinson’s (PD) influencing cognition are functionally connected to the subiculum. However, the results are mixed, and it is unclear how or if DBS site-subiculum connectivity can be optimized to improve patient cognition. Methods: We studied how subiculum connectivity influenced cognitive outcomes in both PD (subthalamic nucleus) and AD (fornix) DBS patients (total n = 110). We first confirmed DBS site-subiculum connectivity had opposite cognitive effects in each disease. We next investigated patient factors underlying these opposing effects. Lastly, we related our findings back to clinical practice to guide DBS programming in PD and AD. Results: DBS site-subiculum connectivity correlated with cognitive improvement in AD but decline in PD. This was dependent upon hippocampal atrophy; such that higher subiculum connectivity was beneficial when the hippocampus was atrophic but deleterious when it was intact. Finally, we related our findings back to anatomy with cadaveric dissections and present how DBS stimulation can be optimized to improve patient cognition. Conclusions: DBS site-subiculum connectivity influences cognition but depends on patient factors. Thus, to optimize cognition based on patient factors, DBS electrodes can be programmed to stimulate subregions with higher or lower subiculum connectivity.

Background: Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) is a rare, acquired polyneuropathy, especially in children, affecting the peripheral nervous system. It most commonly presents in a symmetric, proximal and distal, sensorimotor fashion. Immunosuppression and immunomanipulation are treatment modalities. This is an update of the 14-year-old male presented, at the 2024 CNSF meeting, with severe progressive CIDP who became refractory to steroid and IVIg but responded to Rituximab. Methods: At the age of 16, at a stage of recovery where he had regained MRC grade 5 strength diffusely, all therapies were sequentially tapered (prednisone & IVIg) or withdrawn (rituximab). He did well for approximately 6 months at which point he relapsed severely to the point of needing a walker. Repeat electrodiagnostics confirmed latency, amplitude, and conduction velocity deteriorations as compared to previous. As a result, prednisone, IVIg, and rituximab were reinstated. Results: As per the first exposure to rituximab, the patient began to respond roughly 3 months after the retreatment with targeted anti-CD20 therapy. He has again made a complete recovery physically but not electrophysiologically. This is the same pattern of response that was originally manifested. Conclusions: Rituximab appears to be an effective treatment for severe IVIg-refractory pediatric CIDP.

Background: MLASA (myopathy, lactate acidosis and sideroblastic anemia) is a rare autosomal recessive mitochondrial disorder, which affects oxidative phosphorylation and iron metabolism in skeletal muscle and bone marrow. Three genes have been identified so far, PUS1 is the most common, followed by YARS2 and MT-ATP6. We present a patient with a novel variant in YARS2 and a literature review. Methods: We report a 20-months-old girl with ptosis and low birth weight. She presented with delayed motor milestones and bulbar weakness with feeding difficulties. She had mild anemia and elevated lactate, echocardiogram revealed a mild to moderate left ventricular hypertrophy without LVOT obstruction. Results: Genetic testing showed two heterozygous variants in YARS2. The maternal one (c.948G>T, p. Arg316Ser) has been reported previously in a compound heterozygous state, while the paternal one (c.917T>C, p.Phe306Ser) has not been previously described. Genetic findings were supported by enzyme activities, which showed reduced complex I+III and complex IV activities and reduced cytochrome oxidase (COX). Conclusions: In this case report we describe a 20-months-old girl with clinical features of MLASA. A novel variant in the YARS2 gene was found, pathogenicity could be proven with clinical phenotype and enzyme activity testing.

This article assesses the cultures of assembly in the Dutch global sphere of influence. It focuses on so-called landdagen (‘land days’), formal assemblies of Dutch provincial communities. While originating in the late medieval Low Countries, several such bodies were instituted in Dutch colonies in the seventeenth century. This article is the first to compare contemporary reflections on three such land days, namely that of the province of Guelders in the metropole, and those in New Netherland (North America) and Formosa (now Taiwan) in overseas territories. These three assemblies offer an illuminating case study, for, while differing in some respects, they possessed similar powers in the political structure of the Dutch Republic. This article examines how the Dutch traditions of assembly interacted and/or hybridised with other European parliamentary cultures and Indigenous traditions of assembly in overseas contexts. It argues that early modern Dutch perceptions of the genesis and functions of the landdagen reveal a pragmatic commingling of different assembly traditions, calculated to foster a shared sense of political community.

Roger was a 60-year-old man living with both HIV and schizophrenia who was admitted to the hospital for treatment of a chronic obstructive pulmonary disease exacerbation. He was referred to the psychiatry consultation-liaison team due to persistent psychotic symptoms that had not responded to multiple antipsychotic trials. Roger’s psychiatric history revealed a diagnosis of schizophrenia in early adulthood, marked by hallucinations and delusions of grandeur. Over the next 4 decades, he cycled through jails, prisons, shelters, and periods of homelessness. Though intermittently connected with outpatient care, his illness remained poorly controlled.

Background: Informed consent is not always possible in emergency research particularly during life threatening situations. Deferral of consent is an acceptable method in consenting patients; however, it is underutilized. We aim to share our experience with deferred consent. Methods: Participants in two prospective studies underwent a CT-Perfusion scan (intervention) at the time of first hospital imaging, in order not to impact clinical treatment. Deferred consent was then obtained. The primary outcome was the rate of deferred consent. The number of days to obtain consent, refusal rate, and waiver of consent rate was also reported. Results: A total of 291 patients (200 severe traumatic brain injury [TBI] and 91 out-of-hospital cardiac arrest) were enrolled between the two emergency CT-perfusion studies. Some (34/291[11.9%]) could not be reached; waiver of consent was granted by our ethics board. Deferred consent was obtained in 252/291(86.6%). The majority were consented by the partner/spouse (25.2%) and most consents took place within 7-days (76.0%) of enrollment. Five (1.7%) refused consent. Deferred consent rates were higher in the cardiac arrest population (97.8%) compared to the severe TBI population (83.7%). Conclusions: Deferred consent is an acceptable method of obtaining consent in emergency research when the intervention risk is low.

Here we present the resistance of two halophilic Archaea, Halorubrum (Hrr.) sp. AS12 and Haloarcula (Har.). sp. NS06, isolated from the brine in Lunenburg, Germany, to stress factors including desiccation, radiation and elevated perchlorate concentration. This is the first study to describe the stress resistance of halophilic Archaea isolated from the Lunenburg brine. While Hrr. sp. AS12 tolerates desiccation up to 45 days with a -log3 reduction in survival, Har. sp. NS06 displays a strong decline in viability and no detectable survival following 21 days. In contrast, Hrr. sp. AS12 was more sensitive towards X-Ray irradiation with a significant decline in viability (D10 228,2 ± 8,9 Gy) while Har. sp. NS06 showed a slight decline in survival following exposure to 1 kGy. The resistance of both strains against germicidal UV-C254nm radiation follows a similar pattern when compared to X-ray exposure with Hrr. sp. AS12 displaying more sensitivity to UV-C radiation (F10 111,6 ± 6,4 J/m2) compared to Har. sp. NS06 (F10 194,9 ± 13,7 J/m2). Exposure to He, Ar, and Fe heavy ions up to 500 Gy showed little effect on the survivability; however, the transport control of Hrr. sp. AS12 showed a strong decline (-log3 reduction) in survival. Both strains revealed increased growth in the presence of perchlorates (NaClO4 and MgClO4) with a clear preference to NaClO4 up to 5%. Our results provide a first insight into the stress resistance of these two isolates and will further develop our understanding of the parameters of life on Earth and potentially on other planets.

Background: Recent research has identified the coexistence of normal pressure hydrocephalus (NPH) with neurodegenerative disorders, such as progressive supranuclear palsy (PSP). We present a patient with shunt-responsive NPH that was diagnosed with PSP at autopsy, in the absence of the typical clinical features of PSP antemortem. Methods: Medical records were reviewed, including diagnostic imaging and neuropathology. A literature review was conducted. Results: A 78-year-old female presented with a 4-year history of progressive gait dysfunction and cognitive impairment. MRI imaging was consistent with NPH. The patient’s clinical status improved significantly following high-volume lumbar puncture, with TUG test results decreasing to 25.19 sec from 58.73 sec. A lumboperitoneal shunt was inserted. Subsequent clinical improvement was impermanent, despite the absence of shunt malfunction. Autopsy revealed neuropathological findings consistent with PSP. We have identified 7 similar cases of NPH patients found to have concomitant PSP at autopsy in the literature. Like the case we present, these shunted patients experienced an initial, but unsustained, improvement in clinical status. Conclusions: We recommend the clinical management of NPH patients includesurveillance for neurodegenerative disorders. CSF diversion in NPH patients who develop concomitant PSP benefit from CSF diversion, offering them an interval of significantly improved quality of life.

Background: Spinal muscular atrophy (SMA) is caused by biallelic mutations in the SMN1 gene. Early diagnosis through newborn screening (NBS) and presymptomatic treatment optimize health outcomes. Methods: SMA-NBS began in Alberta on 28February2022. A multiplex quantitative PCR assay detected homozygous deletions of exon 7 in dried blood spot samples. Screen-positive infants underwent genetic confirmation by multiplex ligation-dependent probe amplification to determine SMN1/SMN2 copy numbers. We report clinical outcomes of SMA diagnoses through Alberta NBS over 3 years. Results: From 28February2022-31December2024, twelve infants were confirmed SMA positive, including two with 2 SMN2 copies and six with 3 SMN2 copies. Median age at initial positive screen was 6 days (range=3-9), and at diagnosis, 15 days (range=11-27). Seven infants (median age=29 days, range=18-142) received onasemnogene abeparvovec-xioi. Two received nusinersen (Day 22) or risdiplam (Day 72), followed by onasemnogene abeparvovec-xioi (Day 48 and 111, respectively). Two infants received risdiplam after 3 months of age. One infant was symptomatic at treatment initiation. Post-treatment evaluations showed ongoing motor milestone achievements. Conclusions: SMA incidence in Alberta during 2022-2024 was 8.2 (95%CI: 3.5-12.8) cases per 100,000 live births. Efforts continue to shorten age at treatment initiation, especially for those with two SMN2 copies, and to promote uniform coverage for 4-copy cases.

Background: Over 28% of people with epilepsy (PwE) experience anxiety related to their seizures, yet research on interventions for epilepsy-specific (ES) interictal anxiety remains limited. The community-based pilot, ’AnxEpi-VR,’ tested virtual reality exposure therapy (VR-ET), showing potential effectiveness and laying the groundwork for evaluating its impact on ES-anxiety in the present randomized controlled trial. Methods: Fourteen PwE admitted to the Epilepsy Monitoring Unit at Toronto Western Hospital used a 360-degree VR-intervention twice daily for five minutes up to ten days. The control group (n=7) viewed neutral VR environments (e.g., beach, forest scenes), while the experimental group (n=7) experienced VR-ET targeting ES anxiety (e.g., subway seizure scenarios). Data was collected at baseline, pre and post-VR exposure, post-intervention, and one-month follow-up using self-report questionnaires, semi-structured interviews, and VR-usage metrics. Clinicaltrials.gov NCT06028945. Results: At baseline, 71% of the control group and 83% of the exposure group had a brEASI score ≥7, indicative of an anxiety disorder. Post-intervention, this decreased to 57% and 50%, respectively. The average Fast Motion Sickness rating was 1.29, indicating minimal motion sickness. Of the exposure participants, 71% felt the scenarios simulated their real-world anxiety triggers. Conclusions: VR-ET was well-tolerated in PwE. Future recommendations include diversifying scenarios, adding interactive features, and improving software connectivity.

Background: Dermoid cysts are rare benign intracranial lesions arising from abnormal neuroectodermal folding during embryogenesis. While typically midline, near the sella or posterior fossa, we report an unusual case of a convexity dermoid cyst extending into the sylvian fissure. Methods: A 33-year-old female with a left convexity mass underwent resection, confirming a dermoid cyst. A literature review was also conducted. Results: The patient presented with progressive, intermittent right-sided hand and face paresthesias. CT showed a 4.3 × 4.7 cm hypodense lesion with peripheral calcification contiguous with the calvarium. MRI revealed an extra-axial, T2-hyperintense, T1-hypointense lesion with internal septations extending from the calvarium into the sylvian fissure. Craniotomy achieved gross total resection, revealing a soft lesion with interwoven hair, suggestive of a dermoid cyst. Pathology confirmed a cystic lesion with mature squamous epithelium, keratin, skin appendages, and chronic inflammation. Conclusions: Dermoid cysts are rare intracranial lesions that most commonly occur in the midline. This case highlights a rare convexity dermoid cyst, expanding our understanding of its atypical locations.

Pieris brassicae (Linnaeus, 1758) (Lepidoptera: Pieridae), commonly known as the cabbage butterfly, is a major herbivorous pest causing significant damage to Brassica crops, which are widely cultivated for edible parts and economic uses such as oilseed production. Conventional chemical-based pest control methods pose risks to environmental and human health, prompting interest in sustainable alternatives like biological control using parasitoids. This study evaluated crop damage by P. brassicae larvae and the potential of the larval parasitoid Cotesia vestalis (Haliday, 1834) (Hymenoptera: Braconidae) in managing pest populations. Larvae and fertilized eggs of P. brassicae were collected and reared on four host diets (cabbage, cauliflower, turnip, and generic brassica) under controlled laboratory conditions. Larval growth, feeding behavior, and development were assessed, along with a feeding index for dietary efficiency. Parasitisation was introduced by exposing larvae to adult C. vestalis, and host-parasitoid interactions were statistically analyzed using one-way ANOVA and regression models. Results revealed that larvae had the highest feeding preference and weight gain on brassica, while turnip-fed larvae consumed the least. Parasitisation by C. vestalis significantly suppressed larval development, with a strong correlation between parasitisation rates and reduced host fitness. These findings highlight C. vestalis as a promising biological control agent for P. brassicae, offering an effective and eco-friendly alternative to chemical pesticides. Further research should focus on optimizing C. vestalis mass-rearing protocols and release strategies tailored to diverse Brassica cropping systems to promote sustainable pest management.

Background: Protein phosphorylation is critical in development and tumor progression, but kinase promiscuity limits selective regulation. Alternative transcription start sites (ATSS) and alternative splicing (AS) may generate isoforms with or without the phosphorylation sites, offering a mechanism of precise control. Sonic Hedgehog (Shh) medulloblastoma (MB), the most common pediatric cerebellar tumor, arises from granule neuron precursors (GNPs) via aberrant Shh signaling. Highly proliferative postnatal day 7 (P7) GNPs and MB share transcriptomic and molecular characteristics, acting as a model for further investigation. Here, we examined the regulation of phosphorylation sites in the mRNA level in P7 GNP and MB. Methods: Integrated phosphoproteomics, proteomics, and RNA-Seq datasets were analyzed to identify candidates producing alternative transcripts with phosphorylation changes in murine P7 GNPs and Ptch1+/- MB. Differential isoform expression was validated via RT-qPCR and RNA-FISH. Results: Rnf220 and Septin9 were identified as candidates that utilize ATSS to produce differential isoforms with or without the phosphorylation sites. RT-qPCR and RNA-FISH showed significant upregulation of their long isoforms in Shh MB compared to GNPs. Conclusions: Alternative transcript generation may act as a novel mechanism for regulating phosphorylation in Shh MB. Differential expression of Rnf220 and Septin9 phosphorylated isoforms suggests their involvement in MB development, warranting further functional investigations.

Background: Vasospasm is an important complication of subarachnoid hemorrhage (SAH). Attempts to identify patients at highest risk of vasospasm have not led to practice change. We sought to identify patients at lowest risk of vasospasm by testing the prognostic utility of novel low risk criteria: mean MCA velocities on TCD that peaked and remained below 120 cm/s by the 7th day. Methods: Retrospective observational study of TCD values in patients admitted to The Ottawa Hospital with SAH 2018-2023. The primary outcome was presence of moderate to severe vasospasm (MCA mean velocity >160 cm/s) by day 21. Results: Data were collected on 211 patients, of whom 197 fulfilled inclusion criteria. Only 2 of 104 patients (2%) meeting our low-risk criteria developed the primary outcome, compared to 48 of 93 patients (52%) who did not meet criteria (RR 27). The Negative Predictive Value (NPV) for vasospasm in our low-risk group was 98%. Conclusions: Our low-risk criteria based on TCD patterns in the first 7 days after SAH can identify patients at very low risk of vasospasm with great accuracy. This could inform a future prospective study.

Background: Under Competence by Design (CBD), there are required training experiences (TEs) and entrustable professional activities (EPAs) in the Transition to Practice (TTP) stage. Limited literature exists to support an evidence-based approach to its implementation and evaluation. We created a novel outpatient rotation for PGY5 neurology residents, simulating independent practice and addressing the TTP TEs. Methods: We conducted a needs assessment with informal interviews of senior residents, the program director, and program administrator of our neurology residency program. Guided by Royal College requirements, and available TTP-focused literature, we designed a general neurology clinic run by PGY5 neurology residents. Focuses included increased independence and efficiency, longitudinal follow-up, and applied principles of practice management. Results: Go-live was August 1, 2024. Eight PGY5 residents completed one block, with a second scheduled later in the academic year. Eleven supervisors participated across two sites. Surveys and structured interviews will be used for both groups to evaluate the program, based on the Kirkpatrick Model. Conclusions: Development of a dedicated clinic addressing the TTP TEs in CBD is feasible. Iterative evaluation of the structure, delivery and outcomes of this required TE is critical to ensure that objectives are met and value is added to the residency curriculum.