bluuebunny/crossref_metadata_2025 huggingface dataset:
A new method of 3D direct current resistivity modelling using a long electrode source for forward probing in tunnels
Authors: Hu Daiming , Tezkan Bülent , Yue Mingxin , Yang Xiaodong , Wu Xiaoping
Published: June 2022

The direct current resistivity method has been widely used for the prediction of water‐bearing structures in subway tunnels and mine tunnels. The traditional direct current resistivity uses point electrode sources in tunnels to excite the electric field; potential electrodes are arranged on the back of the tunnel face to measure the position of the anomaly using the apparent resistivity sounding curve. Due to the dimension limitations of the tunnel cavity, the maximum distance of potential electrodes is often restricted. Thus, the exploration depth often cannot cover the target appropriately. Additionally, owing to the inaccessibility of point electrode sources on the tunnel face, point electrode sources can only be set near the tunnel face, so the electric signal excited by point electrode sources cannot be coupled with the water‐bearing anomaly at a large depth. As such the traditional point electrode method for forward probing in tunnels has a shortcoming of small detection depth. To overcome this problem by increasing the detection depth, a horizontal drilling copper casing is first used as a new long electrode source array, which (as far as the authors are aware) has never been reported in forward probing in tunnels. We developed a new method of 3D direct current resistivity modelling with a long electrode source for forward probing in tunnels using the finite‐element method. The long electrode current source was used to replace the conventional point electrode current source, and the observed potential electrodes were respectively arranged in the tunnel floor, tunnel face and horizontal drilling. Theoretical formulas for the long electrode source for the whole‐space direct current method are first applied in forward probing in tunnels. An analytical test for a whole‐space model with the long electrode source has been used to validate the accuracy of the 3D algorithm. Three synthetic geological models for the long electrode source were used to examine the applicability by investigating the detection capability to predict the anomaly. The observed signal of apparent resistivity excited by the long electrode source is stronger than that of the point electrode source because the long electrode source is closer to the anomaly. This new method using the long electrode source greatly improves the resolution of the anomaly, which is of great significance for the safety of the tunnel construction.
A population PK–PD model of YH4808, a novel P‐CAB, and intragastric pH that incorporated negative feedback by increased intragastric pH onto the systemic exposure to YH4808
Authors: Chung Tae Kyu , Lee Hyun A. , Lee Kyeong‐Ryoon , Jang Seong Bok , Yu Kyung‐Sang , Lee Howard
Published: June 2022

YH4808 is a novel potassium‐competitive acid blocker that is under clinical development to treat patients with gastroesophageal reflux disease and peptic ulcer diseases. In this study, the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of YH4808 were modeled in healthy male volunteers who received a single oral dose of YH4808 at 30, 50, 100, 200, 400, 600, and 800 mg or matching placebo and multiple once‐daily oral doses of YH4808 at 100, 200, and 400 mg or matching placebo for 7 days. A population PK–PD model adequately described the time–concentration‐effect profiles of YH4808. The maximum increasing effect of YH4808 on intragastric pH was 4.38, which was higher than the observed maximum increase in intragastric pH after omeprazole at 40 mg (2.2 in pH). The maximum inhibitory effect by the increased intragastric pH on the exposure to repeated YH4808 was 58% from baseline. Monte–Carlo simulation experiments based on the final model showed that YH4808 at 200 mg will produce a higher percentage of time at pH > 4 over 24 h on day 1 than observed value of esomeprazole at 40 mg once‐daily, an active comparator (84.7% time vs. 58.3% time, respectively). Because YH4808 at ≥200 mg resulted in a higher percentage of time at intragastric pH > 4 than seen after once‐daily esomeprazole at 40 mg and YH4808 showed acceptable tolerability at a single‐dose of 30–800 mg, we suggest to test the 200 mg once daily dosage regimen in further clinical trials of YH4808.
The intricacies of identifying equatorial waves
Authors: Knippertz Peter , Gehne Maria , Kiladis George N. , Kikuchi Kazuyoshi , Rasheeda Satheesh Athul , Roundy Paul E. , Yang Gui‐Ying , Žagar Nedjeljka , Dias Juliana , Fink Andreas H. , Methven John , Schlueter Andreas , Sielmann Frank , Wheeler Matthew C.
Published: June 2022

Equatorial waves (EWs) are synoptic‐ to planetary‐scale propagating disturbances at low latitudes with periods from a few days to several weeks. Here, this term includes Kelvin waves, equatorial Rossby waves, mixed Rossby–gravity waves, and inertio‐gravity waves, which are well described by linear wave theory, but it also other tropical disturbances such as easterly waves and the intraseasonal Madden–Julian Oscillation with more complex dynamics. EWs can couple with deep convection, leading to a substantial modulation of clouds and rainfall. EWs are amongst the dynamic features of the troposphere with the longest intrinsic predictability, and models are beginning to forecast them with an exploitable level of skill. Most of the methods developed to identify and objectively isolate EWs in observations and model fields rely on (or at least refer to) the adiabatic, frictionless linearized primitive equations on the sphere or the shallow‐water system on the equatorial ‐plane. Common ingredients to these methods are zonal wave‐number–frequency filtering (Fourier or wavelet) and/or projections onto predefined empirical or theoretical dynamical patterns. This paper gives an overview of six different methods to isolate EWs and their structures, discusses the underlying assumptions, evaluates the applicability to different problems, and provides a systematic comparison based on a case study (February 20–May 20, 2009) and a climatological analysis (2001–2018). In addition, the influence of different input fields (e.g., winds, geopotential, outgoing long‐wave radiation, rainfall) is investigated. Based on the results, we generally recommend employing a combination of wave‐number–frequency filtering and spatial‐projection methods (and of different input fields) to check for robustness of the identified signal. In cases of disagreement, one needs to carefully investigate which assumptions made for the individual methods are most probably not fulfilled. This will help in choosing an approach optimally suited to a given problem at hand and avoid misinterpretation of the results.
Endemic Guadalupe bass (Micropterus treculii) are supported by isotopically distinct resources in tributary versus mainstem river food webs
Authors: Pease Allison A. , Pease Jessica E. , Bean Preston T. , Grabowski Timothy B.
Published: June 2022

We used stable isotope analysis to investigate differences in Guadalupe bass (Micropterus treculii) resource use that might be associated with population‐level variation in mainstem river versus tributary stream habitats. Guadalupe bass from mainstem sites had higher δ13C and δ15N values compared to those collected in tributaries, likely reflecting greater importance of algae as a basal resource and influences of urban wastewater in mainstem habitats. Documenting ecological variation across ecosystem types is important to inform fish conservation efforts, especially for species that occupy a range of stream sizes.
Estimating the longitudinal trajectory of cognitive function measurement using short‐term data with different disease stages: Application in Alzheimer's disease
Authors: Hirakawa Akihiro , Sato Hiroyuki , Hanazawa Ryoichi , Suzuki Keisuke ,   Japanese Alzheimer's Disease Neuroimaging Initiative
Published: June 2022

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by a gradual decline in cognitive function over a few decades. The Mini‐Mental State Examination (MMSE) is a widely used measure for evaluating global cognitive functioning. Characterizing the longitudinal trajectory of the MMSE in the population of interest is important to detect AD onset for preventive intervention. In this study, we formulate a new class of longitudinal trajectory modeling for MMSE from short‐term individual data based on an ordinary differential equation. The proposed method models the relationship between individual decline speed of MMSE and the average MMSE using the fractional polynomial function model and subsequently estimates the longitudinal trajectory of MMSE by solving the ordinary differential equation for the estimated model. The appropriate model for trajectory estimation is selected based on the proposed criterion for quantifying the goodness of trajectory fit. The accuracy of the trajectory estimation of the proposed method was demonstrated via simulation studies. The proposed method was successfully applied to MMSE data from the Japanese Alzheimer's Disease Neuroimaging Initiative study.
Cu‐Doped Polypyrrole with Multi‐Catalytic Activities for Sono‐Enhanced Nanocatalytic Tumor Therapy
Authors: Chen Ting , Zeng Weiwei , Liu Yuanqi , Yu Mian , Huang Chenyi , Shi Zhaoqing , Lin Chuchu , Tang Jia , Mei Lin , Wu Meiying
Published: June 2022

Nanocatalytic medicine is a burgeoning disease treatment model with high specificity and biosafety in which the nanocatalyst is the core of driving catalytic reaction to generate therapeutic outcomes. However, the robust defense systems in the pathological region would counteract nanocatalyst‐initiated therapeutics. Here, a Cu‐doped polypyrrole is innovatively developed by a facile oxidative polymerization reaction, which exhibits intriguing multi‐catalytic activities, including catalyzing H2O2 to generate O2 and ·OH, and consuming reduced glutathione by a Cu(II)‐Cu(I) transition approach. By decorating with sonosensitizers and DSPE‐PEG, the obtained CuPPy‐TP plus US irradiation can induce severe oxidative damage to tumor cells by amplifying oxidative stress and simultaneously relieving antioxidant capacity in tumors based on the highly effective sonochemical and redox reactions. The notable tumor‐specific biodegradability, remarkable cell apoptosis in vitro, and tumor suppression in vivo are demonstrated in this work, which not only present a promising biocompatible antitumor nanocatalyst but also broaden the perspective in oxidative stress‐based antitumor therapy.
Immunomodulatory and Antioxidant Effects of Polysaccharides from Pleurotus ostreatus on Immunosuppressed Mice
Authors: Du Biqi , Zhang Xiao , Zhu Caiping , Wu Yuan , Ji Huijie , Zhang Yifan , Yue Xiaoxia
Published: June 2022

The presented study investigates the immunity activities of Pleurotus ostreatus polysaccharides (POP) in cyclophosphamide (CTX)‐immunosuppressed mice. The CTX‐induced mice are orally administrated with POP at the dosage of 100, 200, and 400 mg kg−1 bodyweight respectively, for 28 days. Experimental results show that POP improves the immune functions of the immunosuppressed mice, retards the decrease in body weight and enhances the immune organ index, and simultaneously increases the T‐lymphocyte proliferation rate. In the POP group, the level of delayed‐type hypersensitivity (DTH), the activity of lactate dehydrogenase (LDH), acid phosphatase (ACP), immunoprotein (Ig‐A, Ig‐G, Ig‐M), cytokines (TNF‐α, IL‐2, INF‐γ), blood parameters (red blood cells, hemoglobin, white blood cells, platelets) are also remarkably improved compared to the CTX group. This study shows that POP exhibits significant antioxidant activity by enhancing catalase (CAT), glutathione peroxidase (GSH‐PX), total antioxidant capacity (T‐AOC), and total superoxide dismutase (T‐SOD), and inversely decreasing the malondialdehyde (MDA) levels. In conclusion, it can be proved that the preventive intervention of POP can enhance the immune function and antioxidant activity in the immunosuppressed mice. These findings may provide a valuable reference for the application of POP in chemotherapy‐induced immunosuppression therapy.
Numerical Bifurcation Analysis of PDEs From Lattice Boltzmann Model Simulations: a Parsimonious Machine Learning Approach
Authors: Galaris Evangelos , Fabiani Gianluca , Gallos Ioannis , Kevrekidis Ioannis , Siettos Constantinos
Published: June 2022

We address a three-tier data-driven approach for the numerical solution of the inverse problem in Partial Differential Equations (PDEs) and for their numerical bifurcation analysis from spatio-temporal data produced by Lattice Boltzmann model simulations using machine learning. In the first step, we exploit manifold learning and in particular parsimonious Diffusion Maps using leave-one-out cross-validation (LOOCV) to both identify the intrinsic dimension of the manifold where the emergent dynamics evolve and for feature selection over the parameter space. In the second step, based on the selected features, we learn the right-hand-side of the effective PDEs using two machine learning schemes, namely shallow Feedforward Neural Networks (FNNs) with two hidden layers and single-layer Random Projection Networks (RPNNs), which basis functions are constructed using an appropriate random sampling approach. Finally, based on the learned black-box PDE model, we construct the corresponding bifurcation diagram, thus exploiting the numerical bifurcation analysis toolkit. For our illustrations, we implemented the proposed method to perform numerical bifurcation analysis of the 1D FitzHugh-Nagumo PDEs from data generated byD1Q3 Lattice Boltzmann simulations. The proposed method was quite effective in terms of numerical accuracy regarding the construction of the coarse-scale bifurcation diagram. Furthermore, the proposed RPNN scheme was$$\sim $$∼20 to 30 times less costly regarding the training phase than the traditional shallow FNNs, thus arising as a promising alternative to deep learning for the data-driven numerical solution of the inverse problem for high-dimensional PDEs.
Land consolidation through parcel exchange among landowners using a distributed Spark-based genetic algorithm
Authors: Teijeiro Diego , Amor Margarita , Doallo Ramón , Corbelle Eduardo , Porta Juan , Parapar Jorge
Published: June 2022

Land consolidation is an essential tool for public administrations to reduce the fragmentation of land ownership. In particular, parcel exchange shows promising potential for restructuring parcel holdings, even more when the number of parcels and owners involved is large. Unfortunately, the number of possible exchange combinations grows very quickly with the number of participating landowners and parcels, with the associated challenge of finding an acceptable solution. In this paper, we present a high-performance solution for parcel exchange based on genetic algorithms. Our proposal, using Apache Spark framework, is based on the exploiting of distributed-memory systems with effortless access in order to reduce the execution time. This also allows increasing the search width through multiple populations that share their advances. This can be achieved without compromising the search depth thanks to the higher amount of resources available from using distributed-memory systems. Our proposal is capable of achieving better solutions in lower amounts of time compared to previous works, showing that genetic algorithms on a high performance system can be used to propose fair parcel exchanges under strict time constraints, even in complex scenarios. The performance achieved allows for fast trial of several options, reducing the time usually needed to perform administrative procedures associated with land fragmentation problems. Specifically, our proposal is capable of combining the benefits of both depth-focused and width-focused multithreaded parallelization. It matches the speedup gains of depth-focused multithreaded parallelization. The width-focused parallelization provides local minimum resilience and fitness value reduction potential. In this paper, multithreading solutions and Spark-based solutions are tested.
Can rainfall seasonality trigger soil water repellency in a tropical riparian forest?
Authors: Brito Gleicon Queiroz de , Murta Johnny Rodrigues de Melo , Mendonça Filho Sérgio Fernandes , Salemi Luiz Felippe
Published: June 2022

Though riparian areas generally have a shallow water table and higher soil moisture compared to upslope areas, climatic seasonality may trigger water repellency in tropical riparian forests, which, if persistent, could negatively affect essential ecosystem functions related to water resources protection such as reduced overland-flow, sediment transport, and nutrient filtration. The objective of this study was to answer the following: can tropical riparian forests develop water repellency? If so, does water repellency affect infiltration on a seasonal basis? For this, water repellency and infiltration were measured in a grid of 72 points during a dry and a wet month of a tropical riparian forest with a shallow water table in a region with highly marked climatic seasonality. Water repellency and infiltration were significantly different between the wet and dry months. Water repellency affected negatively infiltration in the dry month, its effect in the wet month was insignificant. As a result, a higher infiltration capacity was observed over the wet period. Previous research has claimed that the development and persistence of repellency in soils could promote other hydrological processes such as overland flow. The findings shown here demonstrate that such phenomenon does not persist longer than the dry season.
Optimizing coagulation–flocculation processes with aluminium coagulation using response surface methods
Authors: Mensah-Akutteh Hanson , Buamah Richard , Wiafe Samuel , Nyarko Kwabena B.
Published: June 2022

A data-based multivariate method such as response surface methods and desirability function is considered advantageous for analysing coagulation treatment optimization. Thus, this study investigated the optimization of coagulation–flocculation using response surface methodology. The parameters investigated were pH, alum dose and alkalinity. The optimum coagulation conditions for the individual responses: turbidity, colour, residual aluminium and phenanthrene were pH 7.0, alum dose 80.0 mg/L and alkalinity 80.0 mg/L; pH, 6.5, alum dose 70.0 mg/L and alkalinity 90.0 mg/L; pH, 7.0, alum dose 63.2 mg/L and alkalinity 80.0 mg/L and pH 6.2, alum dose 80.0 mg/L and alkalinity of 80.0 mg/L, respectively. The model equation derived from the optimization study was adequate for predicting the response values. The quadratic model was significant (p < 0.0001), and it had a high correlation (R2, 0.746–0.975) and an insignificant (LOF, p > 0.05) lack of fit.
Difference in the neurocognitive functions of WLWH and MLWH in an Italian cohort of people living with HIV
Authors: Donne Valentina Delle , Massaroni Valentina , Ciccarelli Nicoletta , Lombardi Francesca , Borghetti Alberto , Ciccullo Arturo , Dusina Alex , Farinacci Damiano , Baldin Ganmaria , Visconti Elena , Tamburrini Enrica , Di Giambenedetto Simona
Published: June 2022

Based on the available literature, women living with HIV (WLWH) seem to show greater cognitive and emotional disadvantages than men living with HIV (MLWH). Our aim was to compare the cognitive performance of MLWH and WLWH in an Italian cohort of People Living With HIV (PLWH) and to analyse factors potentially contributing to sex differences in cognitive function. We ran a retrospective, cross-sectional analysis of a monocentric dataset of PLWH who were administered a standardized neuropsychological test battery (SNB) during routine clinical care. We enrolled 161 Italian PLWH who are on combined antiretroviral therapy (cART): 114 (70.8%) MLWH and 47 (29.2%) WLWH.

Global cognitive performance (composite z score) (GCP) was significantly higher in MLWH than WLWH [mean 0.19 (SD 0.85) vs − 0.13 (SD 0.96); p = 0.039]. Moreover, WLWH obtained significantly higher scores on the Zung Depression Scale than MLWH [mean 41.8 (SD 10.9) vs 36.7 (SD 9.2); p = 0.003]. However, there was no statistically significant direct effect between male sex and better GCP (p = 0.692) in the context of a mediation model. On the contrary, the associations between male sex and better GCP were mediated by higher level of education (a*b =  + 0.15, Bootstrap CI95 = 0.05 and 0.27) and a lower Zung depression score (a*b =  + 0.10, Bootstrap CI95 = 0.02 and 0.21).

In conclusion, the global cognitive performance of WLWH is lower than that of MLWH. However, other demographic and clinical factors besides sex might help explain differences in their neurocognitive functions and make it possible for us to monitor them and identify those patients most in need.
Witchcraft and Paganism in Midcentury Women's Detective Fiction
Authors: Bloomfield Jem
Published: June 2022

Witchcraft and paganism exert an insistent pressure from the margins of midcentury British detective fiction. This Element investigates the appearance of witchcraft and paganism in the novels of four of the most popular female detective authors of the era: Agatha Christie, Margery Allingham, Ngaio Marsh and Gladys Mitchell. The author approaches the theme of witchcraft and paganism not simply as a matter of content but as an influence which shapes the narrative and its possibilities. The 'witchy' detective novel, as the author calls it, brings together the conventions of Golden Age fiction with the images and enchantments of witchcraft and paganism to produce a hitherto unstudied mode of detective fiction in the midcentury.
P.002 Saccade parameters reveal cognitive impairment and differentially associate with cognitive domains across neurodegenerative diseases
Authors: Riek HC , Coe BC , Brien DC , Huang J , Abrahao A , Arnott S , Beaton D , Binns M , Black S , Borrie M , Casaubon L , Dowlatshahi D , Finger E , Fischer C , Frank A , Freedman M , Grimes D , Hassan A , Jog M , Kumar S , Kwan D , Lang A , Lawrence Dewar J , Levine B , Lou W , Mandzia J , Marras C , Masellis M , McLaughlin P , Orange J , Pasternak S , Peltsch A , Pollock B , Rajji T , Roberts A , Sahlas D , Saposnik G , Seitz D , Shoesmith C , Steeves T , Strother S , Sujanthan S , Sunderland K , Swartz R , Tan B , Tang-Wai D , Tartaglia C , Troyer A , Turnbull J , Zinman L ,   ONDRI Investigators (), Munoz DP
Published: June 2022

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.
P.003 CJD in the modern era: The value of clinical features and diagnostic tests
Authors: Shir D , Lazar EB , Graff-Radford J , Aksamit AJ , Cutsforth-Gregory JK , Jones DT , Botha H , Ramanan VK , Prusinski CC , Porter AL , Day GS
Published: June 2022

Background: The advent of real-time quaking-induced conversion (RT-QuIC) assays has transformed the diagnostic approach to sporadic Creutzfeldt-Jakob disease (CJD) facilitating earlier recognition of affected patients. Recognizing this, we evaluated the performance of clinical features and diagnostic tests for CJD in the modern era. Methods: Clinical data were extracted from the electronic medical records of 115 patients with probable or definite CJD assessed at Mayo Clinic from 2014-2021. Clinical features and diagnostic tests were evaluated at presentation, and associations with diagnosis and prognosis determined. Results: Mean age-at-symptom onset was 64.8±9.4 years; 68 patients were female (59%). The sensitivity of clinical markers (myoclonus) and tests historically considered in patients with suspected CJD was poor (stereotyped EEG abnormalities, 16%; CSF 14-3-3, 60%). Conversely, RT-QuIC (93%), t-tau >1149 pg/mL (88%), and characteristic signal abnormalities on MRI (77%) identified most patients. Multivariable linear regression confirmed shorter days-to-death in patients with myoclonus (125.9, CI95% 23.3-15.5, p=0.026), visual/cerebellar signs (180.19, CI95% 282.2-78.2, p<0.001), positive 14-3-3 (193, CI95% 304.9-82.9; p<0.001), and elevated t-tau (9.0, CI95% 1.0-18.0, for every 1000 pg/ml elevation; p=0.041). Conclusions: CSF RT-QuIC and elevated t-tau, and stereotyped MRI abnormalities were consistently detected in CJD patients. Myoclonus, EEG findings, and CSF protein 14-3-3 were less useful in the modern era.
P.006 Etiologic diagnoses of rapidly progressive dementia in a prospective multicenter cohort
Authors: Day GS , Tipton PW , Lazar E , Martens YA , Dunham S , Geschwind MD , Bu G , Morris JC , Graff-Radford NR
Published: June 2022

Background: Accurate etiologic diagnoses are needed in patients with rapidly progressive dementia (RPD) to ensure access to symptomatic and disease-modifying therapies when available. Methods: Patients with RPD were prospectively enrolled and evaluated at Washington University (Saint Louis, MO; 2016-2019) and Mayo Clinic (Jacksonville, FL; 2020-2021). Etiologic diagnoses were independently assigned by two dementia specialists integrating clinical features and the results of diagnostic tests; disagreements were resolved via blinded review by a third specialist. Results: 160 RPD patients were enrolled and followed. Average age-at-symptom onset was 60.0±15.9 years; 50% were female. Inter-rater reliability (91% agreement; Cohen’s κ=0.88, p<0.001) and clinicopathologic correlation were excellent (100% agreement in 24 patients with neuropathologic data). Autoimmune encephalitis was the leading cause of RPD (39%), followed by Alzheimer disease and related dementias (29%), Creutzfeldt-Jakob disease (15%), and other causes (15%). Patients with potentially treatable causes of RPD were younger (54.5±18.2 than those with neurodegenerative causes (67.3±9.5; p<0.001), and more likely to present with altered levels of consciousness, seizures, or CSF pleocytosis (p<0.05). Conclusions: Etiologic diagnoses can be reliably established in RPD patients using available clinical data. The prevalence of autoimmune encephalitis in this series justifies routine screening for potentially treatment-responsive causes of RPD, particularly in younger patients.
P.012 The new-onset refractory status epilepticus (NORSE/FIRES) family registry
Authors: Kazazian K , Gaspard N , Hirsch LJ , Kellogg M , Hocker SE , Wong N , Farias-Moeller R , Eschbach K , Gofton TE
Published: June 2022

Background: New-onset refractory status epilepticus (NORSE) is a rare clinical presentation affecting previously healthy individuals. Febrile infection-related epilepsy syndrome (FIRES) is a subcategory of NORSE and applies when a preceding fever occurs. The NORSE/FIRES Family Registry has been developed to gain insight into risk factors and to assess the spectrum of clinical outcomes amongst survivors. Methods: Survivors, surrogates, and physicians can enter patient data into the REDCap-based registry: https://www.norseinstitute.org/norse-registry-2. Information collected includes medical history, clinical presentation, and quality of life, among others. Participants are invited to complete follow-up surveys for up to two years following presentation of seizures. Enrollment is ongoing in multiple languages. Results: 56 participants are enrolled from 12 countries (2-78 years, median: 12.5, IQR: 20.5, 31 survivors). At ≥6 months after onset, survivors experience a mean of ≥12 seizures per month and remain on a median of 4 (IQR: 3) anti-seizure medications. The median quality of life amongst all survivors was rated 4/10 (IQR: 3.5). Conclusions: Preliminary data suggests that survivors of NORSE/FIRES have a high seizure burden and poor quality of life. This international multi-lingual family registry will help develop hypotheses for future studies and provides an opportunity for families to contribute to the scientific understanding of this disease.
P.013 Stereo-encephalographic presurgical evaluation of temporal lobe epilepsy
Authors: Paredes-Aragón EM , AlKhaldi N , Ballesteros D , Mirsattari S
Published: June 2022

Background: Drug resistant epilepsy is present in nearly 30% of patients. Resection of the epileptogenic zone has been found to be the most effective in achieving seizure freedom. The study of temporal lobe epilepsy for surgical treatment is extensive and complex. It involves a multidisciplinary team in decision-making with initial non-invasive studies (Phase I), providing 70% of required information to elaborate a hypothesis and treatment plans. Select cases present more complexity involving bilateral clinical or electrographic manifestations, have contradicting information or may involve deeper structures as a part of the epileptogenic zone. Methods: A review of the literature was done with key terms such as: “temporal lobe epilepsy”and “SEEG”and “intracranial EEG”, “epilepsy surgery”, un Pubmed, EMBASE, Medlink and Scielo. Most cutting edge, controversial subjects surrounding this field were considered. Results: In this comprehensive review, we explore the indications, usefulness, discoveries in interictal and ictal findings, pitfalls, and advances in the science of presurgical stereo-encephalography for temporal lobe epilepsy. Conclusions: Intracranial recording follows original concepts since its development by Bancaud and Talairach, but great advances have been made in the field. Stereo-electroencephalography is a growing field of study, treatment and establishment of seizure pattern complexities.
P.040 Value-based approach to the management of Inflammatory Neuropathies: Incorporating objective outcome measures in clinical care
Authors: Smith CB , Chapman K , Mezei M , Beadon K
Published: June 2022

Background: Measuring outcomes that matter to patients is a key component of ensuring patient-centred care. In Chronic Inflammatory Neuropathies (CINs), where immunomodulatory treatments have risks and high costs, systematic evaluation of disease progression is needed to ensure patients are achieving outcomes that reflect their values and goals. The aim of this project is to evaluate the feasibility of objective outcome measure (OOM) use in the clinical setting. Methods: Prospective data was collected from 27 participants with CIDP or MMN. Participants completed and provided feedback on patient-reported outcome measures including quality of life, activity and participation, pain and fatigue, as well as grip strength, 9-hole peg test, 10 meter walk, muscle strength and sensation. Focus groups were conducted to collect qualitative data. Results: The majority of OOMs were considered relevant to 90% of participants. The top three ranked measures were muscle strength testing, daily activities questionnaire and quality of life questionnaire. 52% of participants identified balance and/or detailed gait assessment as an important factor that was not part of collected OOMs. Conclusions: OOMs allow for appropriate monitoring of patients and optimization of immunotherapy treatment. By tracking longitudinal results that matter to patients, patients can better participate in shared-decision making. Clinicians should adopt OOMs going forward.
P.046 Extensive leukoencephalopathy as a differential diagnosis of motor neuron disease: case report and literature review
Authors: Becerra-Mateus JC , Hidalgo-Ramírez MJ , Aguillón-Niño DF , Gómez-Ramírez J , Villegas-Lanau CA
Published: June 2022

Background: Weakness is frequently a reason to attend neurology consultation which entails a challenge due to its wide range of diagnostic possibilities. We present the case of an elderly woman with long-standing right upper limb weakness. Methods: Patient data was obtained from medical records and an extensive neuropathological evaluation was performed. Results: Weakness started off in her right hand, which progressed insidiously to her right hemibody. with hyperreflexia, atrophy, fasciculations and foot drop. Subsequently, bulbar and left hemibody deterioration began. She died due to ventilatory failure four years after the first symptom appeared. A tigroid pattern in the neuroimaging studies suggest white matter involvement, while the neuropathological studies showed loss of motor neurons in the spinal cord. Conclusions: The available evidence does not allow us to dismiss the hypothesis of a motor neuron disease or a leukodystrophy. Cases like this one establish a diagnostic challenge due to their complexity and unusual etiology.
P.050 Understanding the neurocritical care educational needs of trainees
Authors: Bahrami N , McKenzie E , Schoonbaert I , Kromm J
Published: June 2022

Background: Patients with neurological conditions account for 15% of patients admitted to the Intensive Care Unit (ICU). Neurocritical care (NCC) has been proven to reduce mortality, improve functional outcomes and increase patient/family satisfaction. Trainees often lack the knowledge, skills, and experience needed to provide quality NCC. Consequently, timely effective care is compromised, team dynamics suffer, and trainees may experience distress. Methods: To fully understand educational needs, we surveyed University of Calgary residents from various programs who rotate through the Neuro-ICU. Results: Trainees indicated a lack of confidence in their knowledge and skills of most NCC disorders/scenarios in the ICU. While the majority expressed interest in learning NCC, 58% were not aware of the NCC-related competencies outlined for their specialties by the Royal College of Physicians and Surgeons, and 30% had no objectives of their own. Teaching modalities most preferred included patient-centred bedside teaching (96%) and easily accessible resources such as pocket-sized cards (90%) and/or a phone app (96%). Conclusions: Trainees rotating through Neuro-ICU need more accessible and improved learning resources and tools. An NCC curriculum may help improve patient outcomes, team dynamics, and relieve trainee distress.
P.054 Effects of cerebellar Theta Burst Stimulation (TBS) on working memory
Authors: Raies N , Nankoo J , Madan C , Chen R
Published: June 2022

Background: Recent evidence suggests that the cerebellum is involved in cognitive functions. Theta burst stimulation (TBS), a modality of transcranial magnetic stimulation (TMS), on the cerebellum can change its contribution to working memory. Therefore, we hypothesize that excitatory intermittent TBS (iTBS) on the cerebellum would improve performance on working memory tasks, whereas inhibitory continuous TBS (cTBS) would disrupt it. Methods: As this is an ongoing study, nine participants (6 women) took part in this study so far. TBS was applied on the cerebellum bilaterally. All subjects received iTBS, cTBS, and sham iTBS in three sessions in random order. After TBS in each session, participants performed three types of working memory tasks: letter 2-back, digit span forward (DSF), and digit span backward (DSB). Results: The preliminary results suggest that participants performed better in the sham condition in the letter 2-back and the DSB tasks compared to the iTBS and cTBS conditions, but the results did not reach statistical significance due to the small sample size. Conclusions: The preliminary results show that the cerebellar contribution to working memory may be disrupted by TBS. As we gain more statistical power by recruiting more participants, we hope to further demonstrate the effects of cerebellar TBS on working memory.
P.062 Physician approaches to anti-thrombotic therapies, imaging and revascularization for acutely symptomatic carotid stenosis: a hot carotid qualitative study
Authors: Beland B , Ganesh A , Jewett G , Campbell DJ , Varma M , Singh R , Al-Sultan A , Wong J , Menon B
Published: June 2022

Background: There are uncertainties regarding the optimal management of acutely symptomatic carotid stenosis (“hot carotids”). We sought to explore the approaches of stroke physicians to anti-thrombotic management, imaging, and revascularization in patients with “hot carotids”. Methods: We used a qualitative descriptive methodology to examine decision-making approaches of physicians regarding the management of hot carotids. We conducted semi-structured interviews with 22 stroke physicians from various specialties in 16 centers across 4 continents. Results: Important themes regarding anti-thrombotic included limitations of existing clinical trial evidence, competing physician preferences, antiplatelet therapy while awaiting revascularization and various regional differences. Timely imaging availability, breadth of information gained, and surgeon/interventionalist preferences were important themes influencing the choice of imaging modality. The choice of revascularization intervention was influenced by healthcare system factors such as use of multidisciplinary review and operating room/angiography suite availability, and patient factors like age and infarct size. Many themes related to uncertainties in the management of hot carotids were also discussed. Conclusions: Our study revealed themes that are important to international stroke experts. We highlight common and divergent practices while underscoring important areas of clinical equipoise and uncertainty. Teams designing international carotid trials may wish to accommodate identified variations in practice patterns and areas of uncertainty.
P.081 Evolving treatment of pediatric-onset multiple sclerosis in Alberta
Authors: Yearwood C , Wilbur C
Published: June 2022

Background: Pediatric-onset multiple sclerosis (MS) is associated with a high rate of disease activity. However, only a single DMT – fingolimod – has been approved by Health Canada for children, in 2018. In this study, we describe trends in the treatment of pediatric-onset MS in Alberta. Methods: We performed a retrospective review of Alberta administrative health databases, identifying cases of MS under 19 years of age from January 1, 2011 - December 31, 2020. Pharmacy dispenses of MS DMTs were identified by Anatomical Therapeutic Chemical classification code and grouped as injectables (glatiramer acetate, interferon-beta) or newer agents (all others). Results: 79 incident cases of pediatric MS were identified during the study period. 47/79 (59%) had at least one DMT dispense, with the first dispense occurring a median 263 days (IQR 134.5-988) from the index date at a median age of 17.2 years (IQR 16.0-18.6). Injectables accounted for all initial DMT dispenses < 19 years of age prior to 2019, while from 2019-2020 injectables accounted for only 3/15 (20%) initial dispenses, with rituximab (5/15, 33%) being the most common initial DMT in those years. Conclusions: The treatment of children with MS in Alberta has rapidly evolved, shifting shift towards earlier treatment using newer high-efficacy agents.
P.095 Smoking behaviour change is associated with altered functional brain connectivity in older adults
Authors: Thovinakere N , Ai M , Morris T , Noriega de la Colina A , Tremblay-Mercier J , Villeneuve S , Geddes M ,   The PREVENT-AD Research Group ()
Published: June 2022

Background: Smoking is the leading cause of preventable morbidity worldwide and therefore developing effective smoking cessation strategies is a public health priority. However, what brain networks support maintenance of smoking cessation in the long term remains unexplored. Methods: We analyzed the baseline resting-state fMRI data acquired in 23 smokers (Mage = 61.52 ± 3.7) who were followed longitudinally in a cohort of cognitively normal older adults. Self-reported smoking status and amount were recorded at baseline and repeated after 4 years. We investigated the effect of smoking behaviour change on functional brain connectivity using seed-to-voxel approach. We examined a-priori regions of interest (ROIs) including the reward network (ventromedial prefrontal cortex (vMPFC) and ventral striatum) and the right insula. These ROIs are promising target mechanisms given prior behavioural research linking it to smoking cessation. Results: Our results revealed that reduced smoking was associated with reduced connectivity between ventral striatum and middle frontal gyrus and enhanced connectivity between right insula and middle temporal gyrus (voxel p <0.001, cluster p<0.05 FDR corrected). However, change in smoking did not reveal any significant effects in the vMPFC. Conclusions: Our findings suggest that successful smoking behaviour change is associated with altered reward network and insular functional connectivity in the long term.
P.130 Secondary trigeminal autonomic cephalgia due to pituitary adenomas: systematic search of the literature and case illustration
Authors: Alarifi NA , Kowalec P , Beiko J
Published: June 2022

Background: Trigeminal autonomic cephalgias (TAC) have been implicated in a multitude of intracranial mass lesions, including pituitary adenomas. Treatment of the associated pituitary adenoma has been reported to result in resolution of the secondary TAC. Methods: We conducted systematic search of the literature in accordance with PRISMA guidelines using Ovid Medline, Pubmed, Scopus, and Web of Science for TACs with associated pituitary lesions. We searched for all the relevant cases to detail the epidemiology, clinical phenotype of TAC, characteristics of the associated pituitary lesion including its hormonal profile, type of clinical intervention, and outcome. Results: Together with our case, 50 cases are reviewed. Prolactinomas were the most common hormone-producing adenomas (n=35; 71%). Few cases were non-functioning (n=3; 6%). Macroadenomas were predominant (n=30, 70%). Cavernous sinus extension was frequent (n=21; 54%). Medical intervention was the most employed form (n=31; 63%). Surgical intervention was carried in several cases (n=18; 37%). The success rate of medical management was high (n=25/31; 81%). Dopaminergic agonist therapy was the most common medical intervention (n=28; 90%). Conclusions: Secondary TACs with associated pituitary adenomas tend to have debilitating symptoms. The pathophysiology of the association is not entirely clear. Identifying the cause and employing the proper intervention is important to avoid unnecessary suffering.
P.131 Acute subdural hematoma in obstetric patients following epidural anesthesia
Authors: Marciniuk K , Meguro K
Published: June 2022

Background: Post-dural puncture headache is a known complication of neuraxial anesthesia and acute subdural hematoma has been associated with unintentional dural puncture. Notably, a significant number of unintentional dural punctures remain unidentified. We present two contrasting cases of subdural hematoma (SDH) following labour epidural anesthesia with no sign of dural puncture at time of anesthesia. Patient 1 presented with headache post-partum day (PPD) six, SDH was identified PPD23, and blood-patch treatment performed PPD35. Patient 2 presented with headache immediately, had SDH identified PPD3, and placement of blood-patch PPD4. Methods: The cases are presented and the literature was reviewed for prior cases. Results: Patient 1 developed significant bilateral SDH with severe headache and right abducens palsy. Headache resolved post blood patch however surgical evacuation was required and the abducens palsy persisted. Patient 2 experienced resolution of symptoms two days post blood patch, the small unilateral SDH was managed conservatively, and had no neurological deficits. Conclusions: Headache is common in the postpartum period. The majority are primary etiology and benign. SDH is a rare but serious complication of neuraxial anesthesia, and the consequences may be devastating. Rapid identification and early treatment are essential to avoid severe neurological sequelae.
P.138 A small RNA signature from extracellular vesicles in patient plasma correlates with recurrence or progression of high-grade gliomas
Authors: Han J , Attwood K , Roy J , Weeks A
Published: June 2022

Background: While managing patients with high-grade gliomas (HGG), predicting recurrence, or differentiating between pseudoprogression (radiation necrosis) and true tumour progression would be invaluable in improving overall prognosis. Characterizing small RNA (sRNA) expression profiles from plasma-derived extracellular vesicles (EVs) over the course of a patient’s treatments, may allow for patient-specific treatment modifications and improve outcomes. Methods: EVs were isolated using Vn96 capture from plasma obtained longitudinally from HGG patients perioperatively and with routine, follow-up surveillance imaging. sRNA was enriched from the EVs, upon which sequencing and unsupervised hierarchal clustering of sRNA signatures were completed. Expression profiles were grouped longitudinally with the clinical status of patients. Results: Cluster analysis of sequences from nine HGG patients, has revealed a sRNA signature that is able to distinguish between tumours showing evidence of progression and those remaining stable over time. Those samples obtained from patients where a clinical diagnosis of tumour progression or pseudoprogression were uncertain, were found to cluster into progression vs. stable signatures. Clinical follow up of these patients will reveal the predictive value of these identified clusters. Conclusions: These preliminary findings demonstrate the potential utility of small RNA profiling of EVs obtained from patients with high-grade gliomas as non-invasive biomarkers for recurrent/progressive disease or stability/pseudoprogression.
P.141 Primary intracranial melanoma complicated by cerebral venous sinus thrombosis: a case report and literature review
Authors: Mann JA , Yu R , Tso MK
Published: June 2022

Background: Melanocytic tumors of the central nervous system (CNS) such as meningeal melanoma are exceedingly rare tumours derived from leptomeningeal melanocytes. Primary meningeal melanomas account for 0.1% of intracranial neoplasms with an incidence of approximately 0.5 per 10 million. Methods: We report the case of a previously healthy 47 year old male who presented with bilateral tonic-clonic seizure. Magnetic resonance imaging (MRI) demonstrated a homogenously-enhancing right temporal extra-axial lesion. The patient was stabilized on anti-epileptic medications and dexamethasone prior to proceeding with complete surgical resection of the lesion. Review of the current literature was conducted. Results: Macroscopically, the extra-axial lesion was heavily pigmented with invasion of the surrounding dura and skull. Histopathology revealed a poorly differentiated neoplasm with nuclear atypia and melanin-containing cells with strong SOX10 positivity and variable S100 positivity. Systemic workup was negative including absent ocular or cutaneous melanomas. Oncopanel was negative including absent BRAF mutation. He began checkpoint inhibitor therapy and subsequently developed cerebral venous sinus thrombosis (CVST) managed with anticoagulation. At 6 month follow-up, he was neurologically intact, working full-time, and had resumed immunotherapy. Conclusions: Primary intracranial melanoma is a rare tumour that can appear radiographically similar to meningioma. Surgical resection remains the mainstay of therapy for best long-term prognosis.