Background: New Canadian treatment optimization recommendations (TOR) were released in 2020 to guide clinicians on the optimal use of disease modifying treatments (DMTs). The alignment of current practices to TOR was investigated to identify potential areas for improvement in patient care. Methods: From January–July 2021, a chart audit of 160 patients was conducted by a sample of Canadian neurologists. Patient selection criteria included adult patients with relapsing-remitting MS, who had been switched from an initial DMT. Results: In alignment with TOR, most patients received a platform therapy initially (89%; n=143) and suboptimal efficacy response (MRI changes, relapses, disability progression) was the most common trigger for switching treatment. Furthermore, the expanded disability status scale was used in 94% (n=151) of cases during clinical assessment. In some instances, neurologists did not adhere to TOR. Only 10% (n=16) of patients were tested for cognitive function and over half (58%; n=93) did not receive gadolinium contrast at re-baseline MRI. Major criteria for switching therapies based on relapse rate, severity/recovery, or MRI were not followed in (n=4; n=27; n=7) patients respectively. Conclusions: Canadian neurologists are generally aligned with recent TOR for MS. However, they are not switching nearly as often or as early as per TOR criteria.

OBJECTIVES/GOALS: For patients suffering from respiratory failure there are limited options to support gas exchange aside from mechanical ventilation. Our goal is to design, investigate, and refine a novel device for extrapulmonary gas exchange via peritoneal perfusion with perfluorocarbons (PFC) in an animal model. METHODS/STUDY POPULATION: Hypoxic respiratory failure will be modeled using 50 kg swine mechanically ventilated with subatmospheric (10-12%) oxygen. Through a midline laparotomy, two cannulas, one for inflow and one for outflow, will be placed into the peritoneal space. After abdominal closure, the cannulas will be connected to a device capable of draining, oxygenating, regulating temperature, filtering, and pumping perfluorodecalin at a rate of 3-4 liters per minute. During induced hypoxia, the physiologic response to PFC circulation through the peritoneal space will be monitored with invasive (e.g. arterial and venous blood gases) and non-invasive measurements (e.g. pulse oximetry). RESULTS/ANTICIPATED RESULTS: We anticipate that the initiation of oxygenated perfluorocarbons perfusion through the peritoneal space during induced hypoxia will create an increase in hemoglobin oxygen saturation and partial pressure of oxygen in arterial blood. As we expect gas exchange to be occurring in the microvascular beds of the peritoneal membrane, we expect to observe an increase in the venous blood oxygen content sampled from the inferior vena cava. Using other invasive hemodynamic measures (e.g. cardiac output) and blood samples taken from multiple venous sites, a quantifiable rate of oxygen delivery will be calculable. DISCUSSION/SIGNIFICANCE: Peritoneal perfluorocarbon perfusion, if able to deliver significant amounts of oxygen, would provide a potentially lifesaving therapy for patients in respiratory failure who are unable to be supported with mechanical ventilation alone, and are not candidates for extracorporeal membrane oxygenation.

Background: Standardized magnetic resonance imaging (MRI) guidelines published in 2015 by the Europoean MAGNIMS group and in 2016 by the CMSC are important for the diagnosis and monitoring of patients with multiple sclerosis (MS) and for the appropriate use of MRI in routine clinical practice. Methods: Two panels of experts convened to update existing guidelines for a standardized MRI protocol. The MAGNIMS panel convened in Graz, Austria in April 2019. The CMSC NAIMS panel met separately and independently in Newark, USA in October 2019. Subsequently, the MAGNIMS, NAIMS, and CMSC working groups combined their efforts to reach an international consensus Results: The revised guidelines on MRI in MS merges recommendations from MAGNIMS, CMSC, and NAIMS to improve the use of MRI for diagnosis, prognosis and monitoring of individuals with MS. 3D acquisitions are emphasized for optimal comparison over time. Core brain sequences include a 3D-T2wFLAIR for lesion identification and monitoring treatment effectiveness. Gadolinium-based contrast is recommended for diagnostic studies and judicious use for routine monitoring of MS patients. DWI sequences are recommended for PML safety monitoring. Conclusions: The international consensus guidelines strive for global acceptance of a useful and usable standard of care for patients with MS.

The aims of this study were to (1) compare diet quality between patients with heart failure (HF) and age- and sex-matched community-dwelling healthy older adults and (2) determine whether having HF was associated with a lower Healthy Eating Index-2015 (HEI-2015) score and risk of micronutrient deficiency. The HEI-2015 and macro- and micronutrient intakes of patients with HF were compared with healthy older adults (N 102; 55–92 years old; 53 % female). A paired t-test or Wilcoxon singed-rank test, McNemar's test, and conditional logistic regression were used to assess the association between diet quality and HF status. Median values for HEI-2015 and the number of micronutrient deficiency were used to dichotomise into groups in the conditional logistic regression. There was no significant between-group difference in the HEI-2015 total score (P 0⋅059), whereas the whole grain component was lower in patients with HF than in healthy older adults (3⋅1 ± 3⋅5 v. 4⋅5 ± 3⋅1, P 0⋅037; respectively). Total caloric intake was lower in patients with HF than in healthy older adults (1683 ± 595 v. 2104 ± 670 kcal; P < 0⋅001). Patients with HF had a higher average number of micronutrient deficiencies than healthy older adults (4[2, 6] v. 1[0, 4], respectively, P < 0⋅001). Patients with HF had four times higher odds of being in a high micronutrient deficiency group than healthy older adults, controlling for socio-demographics and body mass index (adjusted odds ratio [95 % confidence interval]: 4⋅04[1⋅06, 15⋅41]). Our findings demonstrate that diet quality measured by nutritional intake identifies patients with HF with lower caloric intake and higher micronutrient deficiencies compared with age- and sex-matched healthy older adults.

We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive ( ${>}7 \times 10^{10} {\mathrm{M}}_\odot$ ) central galaxies at $0.25 < z <0.35$ in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics ( $0.6-0.8$ arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at $0.25 < z <0.35$ , as well as hundreds of emission-line sources at $z < 6$ . This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at $z\approx 0.3$ . MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.

Cosmopolitan habitat-forming taxa of algae such as the genus Corallina provide an opportunity to compare patterns of biodiversity over wide geographic scales. Nematode assemblages inhabiting Corallina turves were compared between the south coasts of the British Isles and South Korea. A fully nested design was used with three regions in each country, two shores in each region and replicate samples taken from three patches on each shore to compare differences in the taxonomic and biological trait composition of nematode assemblages across scales. A biological traits approach, based on functional diversity of nematodes, was used to make comparisons between countries, among regions, between shores and among patches. The taxonomic and biological trait compositions of nematode assemblages were significantly different across all spatial scales (patches, shores, regions and countries). There is greater variation amongst nematode assemblages at the scale of shore than at other spatial scales. Nematode assemblage structure and functional traits are influenced by the local environmental factors on each shore including sea-surface temperature, the amount of sediment trapped in Corallina spp. and tidal range. The sea-surface temperature and the amount of sediment trapped in Corallina spp. were the predominant factors determining nematode abundance and composition of assemblages and their functional diversity.

Lowering dietary protein concentration is known to decrease urinary nitrogen (N) losses and increase milk N efficiency in dairy cows, but it may negatively affect animal productivity. Plant-derived essential oils (EO) may alleviate these negative effects by improving the efficiency of rumen fermentation in cows fed reduced feed protein diets. The experiment was conducted to investigate the effects of lowering crude protein (CP) supply alone or in a combination with an EO product on feed intake, milk production and composition, rumen fermentation, total tract digestibility and N utilization in dairy cows. Twenty-one Holstein cows were used in a replicated 3 × 3 Latin square design experiment. Each period consisted of 14 days for adaptation and 14 days for data collection and sampling. Cows were randomly assigned to one of three experimental diets: a 165 g/kg CP diet (control), a 155 g/kg CP diet (LCP) and LCP supplemented with 35 g/day per cow EO (LCPEO). The dry matter (DM) intake was decreased by LCP and LCPEO compared with the control; there was no effect of EO on DM intake. Milk yield and composition and feed efficiency were similar among treatments. Ruminal pH, lactate, ammonia and volatile fatty acids concentrations were not affected by treatment, except increased valerate concentration by LCPEO compared with LCP. The supplementation of EO tended to decrease protozoal counts. The LCP and LCPEO increased total tract digestibility of DM and organic matter and decreased CP digestibility compared with the control. Supplementation with EO did not affect total tract digestibility of dietary nutrients compared with the control or LCP. The LCP and LCPEO decreased urinary and fecal N excretions and increased milk N efficiency; nitrogen losses were not affected by EO. In this study, lowering dietary CP by 10 g/kg decreased urinary and fecal N excretion without affecting productivity. The supplementation of EO to LCP had only minor effects on rumen fermentation and did not affect productivity, digestibility and N excretion in lactating dairy cows.

Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.

Background: NEDA is a composite measure that may ultimately influence clinical decisions concerning switches of disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS) patients. Cohort studies from MS clinics suggest NEDA is not sustained over time in most patients despite DMT but may be limited by referral bias. We investigated NEDA in a population-based RRMS cohort. Methods: We identified all incident cases of RRMS in Olmsted County from 01/01/2000-12/31/2011. Retrospective chart review was conducted to determine persistence of NEDA -following RRMS diagnosis. NEDA failure was defined as new MRI activity, relapse, or expanded disability status scale (EDSS) -worsening. Results: There were 93 incident cases of RRMS with 82 individuals having sufficient follow-up to determine persistence of NEDA. Prior to NEDA failure 44 were not on DMT, 37 were on first-tier, injectable DMT, and 1 received mitoxantrone. NEDA was maintained by 63% at 1 year, 38% at 2 years, 19% at 5 years, and 12% at 10 years. Disability measured by EDSS was no different at 10 years in patients maintaining NEDA versus those that failed NEDA at one year (p=0.3). Conclusions: Maintenance of NEDA beyond 2 years is infrequent among a population-based cohort of newly diagnosed RRMS patients and similar to prior clinic-based cohorts.