Background: ALS is a progressive neurodegenerative disease without a cure and limited treatment options. Edaravone, a free radical scavenger, was shown to slow disease progression in a select group of patients with ALS over 6 months; however, the effect on survival was not investigated in randomized trials. The objective of this study is to describe real-world survival effectiveness over a longer timeframe. Methods: This retrospective cohort study included patients with ALS across Canada with symptom onset up to three years. Those with a minimum 6-month edaravone exposure between 2017 and 2022 were enrolled in the interventional arm, and those without formed the control arm. The primary outcome of tracheostomy-free survival was compared between the two groups, accounting for age, sex, ALS-disease progression rate, disease duration, pulmonary vital capacity, bulbar ALS-onset, and presence of frontotemporal dementia or C9ORF72 mutation using inverse propensity treatment weights. Results: 182 patients with mean ± SD age 60±11 years were enrolled in the edaravone arm and 860 in the control arm (mean ± SD age 63±12 years). Mean ± SD time from onset to edaravone initiation was 18±10 months. Tracheostomy-free survival will be calculated. Conclusions: This study will provide evidence for edaravone effectiveness on tracheostomy-free survival in patients with ALS.

Background: Saccade and pupil responses are potential neurodegenerative disease biomarkers due to overlap between oculomotor circuitry and disease-affected areas. Instruction-based tasks have previously been examined as biomarker sources, but are arduous for patients with limited cognitive abilities; additionally, few studies have evaluated multiple neurodegenerative pathologies concurrently. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with Alzheimer’s disease (AD), mild cognitive impairment (MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, progressive supranuclear palsy, or Parkinson’s disease (PD). Patients (n=274, age 40-86) and healthy controls (n=101, age 55-86) viewed 10 minutes of frequently changing video clips without instruction while their eyes were tracked. We evaluated differences in saccade and pupil parameters (e.g. saccade frequency and amplitude, pupil size, responses to clip changes) between groups. Results: Preliminary data indicates low-level behavioural alterations in multiple disease cohorts: increased centre bias, lower overall saccade rate and reduced saccade amplitude. After clip changes, patient groups generally demonstrated lower saccade rate but higher microsaccade rate following clip change to varying degrees. Additionally, pupil responses were blunted (AD, MCI, ALS) or exaggerated (PD). Conclusions: This task may generate behavioural biomarkers even in cognitively impaired populations. Future work should explore the possible effects of factors such as medication and disease stage.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Invasive parasites can spill over to new hosts in invaded ecosystems with often unpredictable trophic relationships in the newly arising parasite-host interactions. In European seas, the intestinal copepod Mytilicola orientalis was co-introduced with Pacific oysters (Magallana gigas) and spilled over to native blue mussels (Mytilus edulis), with negative impacts on the condition of infected mussels. However, whether the parasite feeds on host tissue and/or stomach contents is yet unknown. To answer this question, we performed a stable isotope analysis in which we included mussel host tissue and the primary food sources of the mussels, microphytobenthos (MPB) and particulate organic matter (POM). The copepods were slightly enriched in δ15N (mean Δ15N ± s.d.; 1·22 ± 0·58‰) and δ13C (Δ13C 0·25 ± 0·32‰) with respect to their host. Stable isotope mixing models using a range of trophic fractionation factors indicated that host tissue was the main food resource with consistent additional contributions of MPB and POM. These results suggest that the trophic relationship of the invasive copepod with its mussel host is parasitic as well as commensalistic. Stable isotope studies such as this one may be a useful tool to unravel trophic relationships in new parasite-host associations in the course of invasions.

Background: The purpose of this study was to: 1) describe current non-invasive ventilation (NIV) usage patterns amongst Canadian ALS healthcare providers; 2) compare/contrast with previous practice patterns; and 3) explore barriers to NIV access encountered by current practitioners. Methods: Healthcare professionals (including physicians, respiratory therapists, and nurses) at major Canadian ALS care centres were sent a web-based survey. Participants were asked to provide input on practice demographics, access and initiation of NIV, and follow-up of NIV. Quantitative data were analyzed with descriptive and comparative statistics, while qualitative data were analyzed using interpretative phenomenological analysis method to identify emergent themes. Results: 26 participants responded. Median NIV usage was 39% (range 10-100%), about double of what was previously reported (18%). Mean times from referral to routine and urgent NIV initiation were 13 (95% CI 9-17) and 5 (95% CI 3-7) days respectively. NIV was most commonly initiated in clinic (68%), while 38% report having access to home-NIV initiation. Lack of social support (62%) and cognitive impairment (46%) were the most common deterrents to initiating NIV. Similar to what is previously reported, barriers to access can be stratified to patient, clinical, institutional, and regional levels. Conclusions: Despite increased usage and improved access, there remain considerable barriers for ALS patients to receive NIV.

Scandinavian/Canadian high-level nuclear waste repository conditions are expected to evolve from initially warm and oxic to eventually cool and anoxic. During the warm oxic period, corrosion products will accumulate on the container surface. These deposits could impede the reaction of Cu with aqueous sulphide, the only reaction that could lead to the significant accumulation of additional corrosion damage under the long-term anoxic conditions. The kinetics of reaction of Cu with aqueous sulphide solutions have been studied using electrochemical and surface analytical techniques. Corrosion potential measurements were used to follow the evolution of the surface as oxides/hydroxides were converted to sulphides in the sulphide concentration range 10-5 to 10-3 mol/L. Changes in composition were followed by in-situ Raman spectroscopy. Of critical importance is whether or not a period of preoxidation of a Cu container surface can prevent subsequent reaction of the surface with remotely produced sulphide

A model for acidity within pores within corrosion products on anodically-dissolving UO2 was developed using Comsol Multiphysics 3.2 to complement ongoing electrochemical measurements. It was determined that a depression of pH within pores can be maintained if: electrochemically measured dissolution currents used in the calculations are attenuated to reflect very localized pores; corrosion potentials exceed -250 mV (vs. SCE); and pore depths are > 1 μm for 300 mV or >100 μm for -50 mV (vs. SCE). Mixed diffusional-chemical equilibria control is suggested through deviations in the shapes between pH-potential and pH-pore depth plots.

Four milking regimes using automatic cluster removers (ACR) were tested over a 19-week period, from mid to late lactation. Each treatment group consisted of 16 slow-milking cows. The milking regimes used were: an ACR setting of 200 ml/min (Control); raised ACR setting from 200 to 500 in steps of 100 ml/min (Raised ACR); raised ACR as above in conjunction with pre-milking teat stimulation (Raised ACR+Stim); and terminating the milking when an ACR threshold of 200 ml/min was reached or when a predetermined maximum milking duration was reached (Timer). All incremental treatments were applied in blocks of 6 or 7 weeks duration. ACR thresholds were raised from 200 to 500 ml/min without observed loss of milk production when compared with controls. However, even up to an ACR setting of 500 ml/min there was little reduction in the group milking duration even when used with teat stimulation. In contrast, the Timer treatment resulted in a 34% reduction of the maximum milking duration for the group without significant loss of milk yield. For all groups, including Control, strip yield was occasionally very high and highly variable. Willingness of cows to enter the milking platform, behaviour during milking, teat condition and incidence of mastitis were similar for all treatment groups. The results indicated that simple truncation of milking at a predetermined maximum duration could be a most potent and inexpensive method of milking a herd more quickly. Such a method could be employed by using a simple timer in any dairy regardless of the level of sophistication of the milking system.