bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 1 study to assess the absolute bioavailability, mass balance, pharmacokinetics, metabolism, and excretion of [14C]-mobocertinib, an oral inhibitor of EGFR exon 20 insertion mutations, in healthy participants
Authors: Hanley Michael J. , Zhang Steven , Griffin Robert , Zhu Sean Xiaochun , Fram Robert J. , Lin Jianchang , Venkatakrishnan Karthik , Gupta Neeraj
Published: May 2024

Mobocertinib (TAK-788) is a first-in-class oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that received accelerated approval for the treatment of patients with non-small cell lung cancer with EGFR exon 20 insertion mutations previously treated with platinum-based chemotherapy. This phase 1, 2-period, study was conducted to assess the absolute bioavailability of mobocertinib (Period 1), as well as mass balance, pharmacokinetics, metabolism, and excretion of [14C]-mobocertinib (Period 2) in healthy adult males. In Period 1, participants received a single oral capsule dose of 160 mg mobocertinib, followed by a 15-minute intravenous infusion of 50 µg (~ 2 µCi) [14C]-mobocertinib administered from 3.75 to 4 h after the capsule dose. In Period 2, a single oral dose of 160 mg (~ 100 µCi) [14C]-mobocertinib was administered as an oral solution. The geometric mean absolute bioavailability of mobocertinib was determined to be 36.7%. After oral administration of [14C]-mobocertinib, mobocertinib and its active metabolites, AP32960 and AP32914, were minor components in plasma, accounting for only 0.275% of total plasma radioactivity as the majority of mobocertinib-related material was covalently bound to plasma proteins. The geometric mean percentage of the administered radioactive dose recovered in the urine and feces was 3.57% and 76.0%, respectively. Only 0.39% of the oral dose of [14C]-mobocertinib was recovered in the urine as mobocertinib; thus, indicating that renal excretion of unchanged drug was a very minor pathway of elimination. In both treatment periods, mobocertinib was generally safe and well-tolerated as all adverse events were Grade 1 in severity. (Trial registration number ClinicalTrials.gov NCT03811834. Registration date January 22, 2019).
The broken windows theory applies to technical debt
Authors: Levén William , Broman Hampus , Besker Terese , Torkar Richard
Published: May 2024

Context:

The term technical debt (TD) describes the aggregation of sub-optimal solutions that serve to impede the evolution and maintenance of a system. Some claim that the broken windows theory (BWT), a concept borrowed from criminology, also applies to software development projects. The theory states that the presence of indications of previous crime (such as a broken window) will increase the likelihood of further criminal activity; TD could be considered the broken windows of software systems.

Objective:

To empirically investigate the causal relationship between the TD density of a system and the propensity of developers to introduce new TD during the extension of that system.

Method:

The study used a mixed-methods research strategy consisting of a controlled experiment with an accompanying survey and follow-up interviews. The experiment had a total of 29 developers of varying experience levels completing system extension tasks in already existing systems with high or low TD density.

Results:

The analysis revealed significant effects of TD level on the subjects’ tendency to re-implement (rather than reuse) functionality, choose non-descriptive variable names, and introduce other code smells identified by the software tool , all with at least $$95\%$$

95
%

credible intervals.

Coclusions:

Three separate significant results along with a validating qualitative result combine to form substantial evidence of the BWT’s existence in software engineering contexts. This study finds that existing TD can have a major impact on developers propensity to introduce new TD of various types during development.
Life cycle sustainability assessment method for concrete
Authors: Choi Wonyoung , Tae Sungho
Published: May 2024

This study aimed to develop a life cycle sustainability assessment method for concrete. An environmental impact assessment method was developed using the ELCA technique announced through the ISO 14,040 Series and KOLID, one of the life cycle impact assessment indicators. A life cycle cost assessment method was developed based on the unit price of materials and energy consumption according to the Korea Price Information. A Social Impact Assessment Method was developed by identifying appropriate major social topics and analyzing those suggested by the international organizations (UNEP). In accordance with the ‘Towards a Life Cycle Sustainability Assessment’ proposed by UNEP/SETAC, a Sustainable Concrete Index (SCI) was developed that integrates environmental, economic, and social aspects. In addition, the environmental impact of Korea’s 544 concrete types was classified by compressive strength, and the mode value was proposed as a standard concrete (environmental impact 6,662–10,785 KRW(5.02–8.12 USD), production cost 66,549–79,030 KRW(50.13–59.53 USD) so that it could be compared with the assessment concrete. As a result of selecting one ready-mix concrete business place in Korea and conducting a case study by comparing it with standard concrete, EI, CI, SI, and SCI, were analyzed to be 1.135, 1.134, 0.830, and 1.033, respectively, making it possible to quantitatively evaluate concrete sustainability.
Categorial Representation Anew: What are the Categorial Representative Contents that Make Knowledge Possible?
Authors: Spano Nicola
Published: May 2024

In the present article, I address the issue of categorial representative contents, which, according to Husserl’s phenomenological theory, make knowledge possible by providing fullness to intuitive categorial acts. First, I discuss Husserl’s assertion that he no longer approves of his theory of categorial representation developed in Logical Investigations. I argue that the influential interpretation of Husserl’s self-criticism advanced by Dieter Lohmar is unfortunately misleading, as Husserl does not actually claim that categorial representatives are contents of reflection belonging to the realm of inner sensibility, as Lohmar contends. After offering an alternative view of Husserl’s authentic position in Logical Investigations, I examine other possible reasons for his later dissatisfaction. These reasons relate to Husserl’s changing views on the role of categorial representatives in empty thinking acts—necessarily involved in cognition—and the necessity of spontaneously repeating the passive synthesis between the intentional matters that function as categorial representatives in the predicative activity yielding knowledge.
Online Bilateral Predictive Control for Time-Delayed Teleoperation of Snake-like Robots
Authors: Ebrahimian Mahdi , Pourmokhtari Mina , Ghiyasi Morteza , Yazdankhoo Behnam , Beigzadeh Borhan
Published: May 2024

Controlling the teleoperation of snake-like robots is challenging due to complex nonlinear dynamics and communication delays. This research proposes an online bilateral predictive control architecture to address these issues. This control structure is established by predicting environment force and the user’s future motion. The former uses a model-mediated approach by creating a virtual environment on the master side and the latter adopts an artificial neural network (ANN) for online operator’s motion prediction. The slave controller utilizes transmitted data from ANN to generate required backbone lengths, which are then transformed into the slave's local bending and torsional degrees of freedom through the inverse kinematics of the robot. Motion prediction is examined in two scenarios: when the ANN predicts the trained motions, and when it predicts a different motion. Simulation studies demonstrate that the proposed online bilateral predictive teleoperation structure successfully achieves real-time position synchronization and force feedback, by effectively bypassing communication delays.
Ti3C2Tx MXene/reduced graphene oxide/cellulose nanocrystal-coated cotton fabric electrodes for supercapacitor applications
Authors: Duygun İnal Kaan , Bedeloğlu Ayşe
Published: May 2024

Textile-based electrodes are the most important components of wearable and portable supercapacitors. Ti3C2Tx MXene and reduced graphene oxide (rGO) have a great potential for the fabrication of high-performance textile supercapacitor electrodes. In this work, rGO was synthesized with the presence of cellulose nanocrystal (CNC) and Ti3C2Tx/rGO/CNC dispersions with different rGO/CNC contents were prepared. The plain-woven cotton fabrics were coated by homogenous Ti3C2Tx and Ti3C2Tx/rGO/CNC dispersions (5% wt., 15% wt., 30% wt. and 50% wt. rGO/CNC content) and characterized by X-ray Diffraction, Fourier Transform Infrared spectroscopy and Scanning Electron Microscopy techniques. The electrochemical characterization techniques showed that Ti3C2Tx/rGO/CNC loaded fabric electrodes up to 15 wt.% rGO/CNC content exhibited a high specific capacitance of 501.1 F g−1 at a current density of 0.3 A g−1 with low internal electrode resistance, and a good electrochemical stability. The results also showed that MXene/rGO/CNC based high-performance textile supercapacitor electrodes can be prepared by simple drop-casting method.

Graphical Abstract
ON THE REDUCTION OF SOME GENERAL RICCATI-TYPE EQUATIONS
Authors: Hetmaniok Edyta , Różański Michał , Smuda Adrian , Szymura Monika , Wituła Roman
Published: May 2024

The first part of the paper presents a unique reduction of some general Riccati-type differential equation to the general Bernoulli-type equation. Furthermore four special theorems on reduction of some Riccati-type differential equations are considered in the second part of the paper. A number of examples are also presented to illustrate the considered issues.
Evaluating feature attribution methods in the image domain
Authors: Gevaert Arne , Rousseau Axel-Jan , Becker Thijs , Valkenborg Dirk , De Bie Tijl , Saeys Yvan
Published: May 2024

Feature attribution maps are a popular approach to highlight the most important pixels in an image for a given prediction of a model. Despite a recent growth in popularity and available methods, the objective evaluation of such attribution maps remains an open problem. Building on previous work in this domain, we investigate existing quality metrics and propose new variants of metrics for the evaluation of attribution maps. We confirm a recent finding that different quality metrics seem to measure different underlying properties of attribution maps, and extend this finding to a larger selection of attribution methods, quality metrics, and datasets. We also find that metric results on one dataset do not necessarily generalize to other datasets, and methods with desirable theoretical properties do not necessarily outperform computationally cheaper alternatives in practice. Based on these findings, we propose a general benchmarking approach to help guide the selection of attribution methods for a given use case. Implementations of attribution metrics and our experiments are available online (https://github.com/arnegevaert/benchmark-general-imaging).

Graphical abstract
Dimensional reduction formulae for spectral traces and Casimir energies
Authors: Strohmaier Alexander
Published: May 2024

This short letter considers the case of acoustic scattering by several obstacles in $$\mathbb {R}^{d+r}$$

R

d
+
r

for $$r,d \ge 1$$

r
,
d
≥
1

of the form $$\Omega \times \mathbb {R}^r$$

Ω
×

R

r

, where $$\Omega $$
Ω
is a smooth bounded domain in $$\mathbb {R}^d$$

R

d

. As a main result, a von Neumann trace formula for the relative trace is obtained in this setting. As a special case, we obtain a dimensional reduction formula for the Casimir energy for the massive and massless scalar fields in this configuration $$\Omega \times \mathbb {R}^r$$

Ω
×

R

r

per unit volume in $$\mathbb {R}^r$$

R

r

.
Predicting post-surgical functional status in high-grade glioma with resting state fMRI and machine learning
Authors: Luckett Patrick H. , Olufawo Michael O. , Park Ki Yun , Lamichhane Bidhan , Dierker Donna , Verastegui Gabriel Trevino , Lee John J. , Yang Peter , Kim Albert , Butt Omar H. , Chheda Milan G. , Snyder Abraham Z. , Shimony Joshua S. , Leuthardt Eric C.
Published: May 2024

Purpose

High-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care.

Methods

Adult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of resting state network connectivity (FC), tumor location, and tumor volume were used to train a random forest classifier to predict functional outcomes based on Karnofsky Performance Status (KPS < 70, KPS ≥ 70).

Results

The models achieved a nested cross-validation accuracy of 94.1% and an AUC of 0.97 in classifying KPS. The strongest predictors identified by the model included FC between somatomotor, visual, auditory, and reward networks. Based on location, the relation of the tumor to dorsal attention, cingulo-opercular, and basal ganglia networks were strong predictors of KPS. Age was also a strong predictor. However, tumor volume was only a moderate predictor.

Conclusion

The current work demonstrates the ability of machine learning to classify postoperative functional outcomes in HGG patients prior to surgery accurately. Our results suggest that both FC and the tumor’s location in relation to specific networks can serve as reliable predictors of functional outcomes, leading to personalized therapeutic approaches tailored to individual patients.
Flood vulnerability assessment in rural and urban informal settlements: case study of Karonga District and Lilongwe City in Malawi
Authors: Mwalwimba Isaac Kadono , Manda Mtafu , Ngongondo Cosmo
Published: May 2024

Flood vulnerability assessment (FVA) informs the disaster risk reduction and preparedness process in both rural and urban areas. However, many flood-vulnerable regions like Malawi still lack FVA supporting frameworks in all phases (pre-trans-post disaster). Partly, this is attributed to lack of the evidence-based studies to inform the processes. This study was therefore aimed at assessing households’ flood vulnerability (HFV) in rural and urban informal areas of Malawi, using case studies of Traditional Authority (T/A) Kilupula of Karonga District (KD) and Mtandire Ward in Lilongwe City (LC). A household survey was used to collect data from a sample of 545 household participants. Vulnerability was explored through a combination of underlying vulnerability factors (UVFs)-physical-social-economic-environmental and cultural with vulnerability components (VCs)-exposure-susceptibility and resilience. The UVFs and VCs were agglomerated using binomial multiple logit regression model. Variance inflation  factor (VIF) was used to check the multicollinearity of variables in the regression model. HFV was determined based on the flood vulnerability index (FVI). The data were analysed using Multiple Correspondence Analysis (MCA), artificial neural network (ANN) and STATA. The results reveal a total average score of high vulnerability (0.62) and moderate vulnerability (0.52) on MCA in T/A Kilupula of Karonga District and Mtandire Ward of Lilongwe City respectively. The FVI revealed very high vulnerability on enviroexposure factors (EEFs) ($$0.9$$

0.9

) in LC and$$(0.8$$

(
0.8

) in KD, followed by ecoresilience factors (ERFs) (0.8) in KD and$$(0.6$$

(
0.6

) in LC and physioexposure factors (PEFs) ($$0.5)$$

0.5
)

in LC besides 0.6 in KD for the combined UVFs and VCs. The study concludes that the determinants of households’ flood vulnerability are place settlement, low-risk knowledge, communication accessibility, lack of early warning systems, and limited access to income of household heads. The study recommends that an FVA framework should be applied to strengthen the political, legal, social, and economic responsibilities of government for building the resilience of communities and supporting planning and decision-making processes in flood risk management.
Evaluating the latest trends of Industry 4.0 based on LDA topic model
Authors: Ozyurt Ozcan , Özköse Hakan , Ayaz Ahmet
Published: May 2024

This study employs the Latent Dirichlet allocation method, a topic modeling technique, to reveal hidden patterns in Industry 4.0 research. The dataset comprises 8584 articles published in the Scopus database from 2011 to the end of 2022. The analysis categorized the articles into 12 distinct topics. The three most prominent topics identified are “Smart Cyber-Physical Systems,” “Digital Transformation and Knowledge Management” and “Data Science in Energy,” respectively. The findings from this topic modeling provide a comprehensive overview for researchers in the field of Industry 4.0, offering valuable insights into current trends and potential future research directions.
The Monstrous Conclusion
Authors: Stroppa Luca
Published: May 2024

This paper introduces the Monstrous Conclusion, according to which, for any population, there is a better population consisting of just one individual (the Monster). The Monstrous Conclusion is deeply counterintuitive. I defend a version of Prioritarianism as a particularly promising population axiology that does not imply the Monstrous Conclusion. According to this version of Prioritarianism, which I call Asymptotic Prioritarianism, there is diminishing marginal moral importance of individual welfare that can get close to, but never quite reach, some upper limit. I argue that Asymptotic Prioritarianism faces a theoretical cost, that I call the Absolute Priority Principle. However, the Absolute Priority Principle is an extreme version of what I call the Trade-off Condition, an already noteworthy problem facing other (more widely endorsed) versions of Prioritarianism. I conclude that it is better for a theory to imply the Absolute Priority Principle and avoid the Monstrous Conclusion than to imply the Monstrous Conclusion and the Trade-off Condition. The potential for Asymptotic Prioritarianism is substantial.
Novel approaches to improve rooting of microshoots, acclimatization and plant growth of Pyrodwarf pear rootstock
Authors: Nawandish Farangis , Dumanoğlu Hatice , Sarıkamış Gölge
Published: May 2024

Ex vitro root formation of micro cuttings of Pyrodwarf pear rootstock (Pyrus communis L.) using floating perlite bed and the effects of Indole-3-butric acid (IBA) treatments on the growth performance after five months were determined. Micro cuttings were dipped in 25, 50, 100 or 150 mg L–1 IBA solutions for 10 s for ex vitro rooting, except for the control. The floating perlite bed cultures were kept for 4 weeks at 25 ± 2ºC with a photoperiod of 16 h light (35 μmol∙m−2∙s−1). At the end of the rooting experiment, there were no statistically significant differences among treatments in terms of rooting percentages (77.8%-81.1%), number of roots (1.9–2.5) and the length of the longest root (22.8–36.8 mm). In the plant growth experiment, ex vitro rooted micro cuttings treated with 25 and 50 mg L–1 IBA and the control were maintained under greenhouse conditions for 5 months to determine the growth performance of the plants. Growth performance was higher in terms of stem diameter, root and stem dry weights of plants rooted with 50 mg L–1 IBA determined as 4.5 mm, 196.5 mg and 704.7 mg, respectively. In conclusion, it was found that the floating perlite bed method was effective in ex vitro rooting and acclimatization. Ex vitro rooting with 50 mg L−1 IBA improved plant growth performance in greenhouse.
Effects of temperature and moisture fluctuations for suitable use of raw-crushed wind-turbine blade in concrete
Authors: Revilla-Cuesta Víctor , Hurtado-Alonso Nerea , Manso-Morato Javier , Serrano-López Roberto , Manso Juan M.
Published: May 2024

Raw-crushed wind-turbine blade (RCWTB), a waste from the recycling of wind-turbine blades, is used as a raw material in concrete in this research. It contains not only fiberglass-composite fibers that bridge the cementitious matrix but also polyurethane and balsa-wood particles. Therefore, concrete containing RCWTB can be notably affected by moisture and temperature fluctuations and by exposure to high temperatures. In this research, the performance of five concrete mixes with 0.0%, 1.5%, 3.0%, 4.5%, and 6.0% RCWTB, respectively, is studied under moist/dry, alternating-sign-temperature-shock, and high-temperature-shock tests. Two damage mechanisms of RCWTB within concrete were found through these tests: on the one hand, micro-cracking of the cementitious matrix, which was verified by microscopic analyses and was dependent on concrete porosity; on the other, damage and degradation of the RCWTB components, as the polyurethane melted, and the balsa-wood particles burned. Both phenomena led to larger remaining-strain levels and reduced concrete compressive strength by up to 25% under temperature and humidity variations, although the bridging effect of the fiberglass-composite fibers was effective when adding RCWTB amounts higher than 3.0%. The compressive-strength loss after the high-temperature-shock test increased with the RCWTB content, reaching maximum values of 8% after an exposure time of 7 days. Statistical analyses revealed that effect of the RCA amount in the concrete was conditioned by the exposure times in all the tests. The accurate definition of those times is therefore key to set an RCWTB content in concrete that ensures its suitable behavior under the environmental conditions analyzed.
Life cycle assessment as a driver for process optimisation of cellobiose lipids fermentation and purification
Authors: Oraby Amira , Briem Ann-Kathrin , Bippus Lars , Rupp Steffen , Zibek Susanne
Published: May 2024

Purpose

Cellobiose lipids (CL) are biosurfactants produced by various Ustilaginaceae species in aerobic fermentations. They show high potential for application as alternatives to conventional oleochemical- or petrochemical surfactants. To ensure their environmentally friendly performance, we aimed to assess CL production from a life cycle perspective at an early developmental stage to identify process steps that have the highest impact on the environment. With this information, optimisation approaches can be derived.

Materials and methods

Following a cradle-to-gate approach, we modelled the CL fermentation and purification process based on experimental data from the lab scale and process simulation data at a 10 m3 scale. For LCA, the impact categories (IC) abiotic depletion potential (ADP), eutrophication potential, photochemical ozone creation potential, global warming potential, acidification potential, and the primary energy demand were calculated for all process steps. Based on the obtained results, process bottlenecks were identified, and alternative process scenarios varying the related process parameters were simulated. These were used to assess the environmental impact reduction potential (EIRP) of an optimised process and draw recommendations for experimental process optimisation.

Results and discussion

The obtained results showed that the fermentation caused ~ 73% of ADP and more than 85% of all other ICs. The major contributor was the electricity consumption for continuous fermenter aeration. Thus, reducing the fermentation duration from the initial 14 to 5 days would result in a decrease in all investigated ICs of up to ~ 27–52%. An increase in CL concentration results in a decrease in all ICs of a similar magnitude due to the higher yield per batch at comparable energy and material consumption. Although the share of purification process steps to all ICs is overall relatively small, implementing foam fractionation for in situ product recovery showed an additional EIRP of 18–27% in all purification IC shares.

Conclusions

The conducted LCA showed that overall, more EIRP can be achieved by optimising fermentation process parameters compared to purification process steps. This is mainly due to the long fermentation duration and large energy consumption for fermenter aeration. This highlights the importance of using LCA as a driver for process optimisation to identify process steps with high EIRP. While some of the results are specific to CL, other obtained results can be transferred to other fermentations.
Conducting sustainability research in the anthropocene: toward a relational approach
Authors: Böhme Jessica , Spreitzer Eva-Maria , Wamsler Christine
Published: May 2024

Scholars and practitioners are urgently highlighting the need to apply a relational approach to effectively address societal crises. At the same time, little is known about the associated challenges, and there is little advice regarding how to operationalize this approach in sustainability science. Against this background, this article explores how we can break out of our current paradigms and approaches, and instead apply relational thinking, being, and acting in the way we conduct research. To achieve this, we systematically list all major research phases, and assess possible pathways for integrating a relational paradigm for each step. We show that moving toward a relational paradigm requires us to methodically question and redefine existing theories of change, concepts, and approaches, for instance by combining abductive reasoning, first-person inquiries, and decentering the human through critical complexity theory. Challenging mainstream thought, and daring to ask different questions in each step is crucial to ultimately shift scientific norms and systems. Hence, we offer a catalog of questions that may help to systematically integrate relational being, thinking, and acting into the process, as a tool for transforming current paradigms in research, and associated education and practice. Finally, we highlight the importance of further research to develop and refine our outcomes.
The mediating role of positive body image
between friendship qualities, well-being strategies and identity development among
adolescents
Authors: Eryılmaz Ali , Kara Ahmet , Uzun Abdullah Ensar
Published: May 2024

This study aimed to explore the mediating role of body image in the
association between The utilization of strategies aimed at enhancing subjective
well-being, friendship qualities, and identity development. The participants
consisted of 270 early adolescents, comprising 157 girls (58.15%) and 113
boys (41.85%). Data were collected using several scales, including the
“Body Appreciation Scale,” “Subjective Well-Being Increasing
Strategies Scale for Adolescents,” “Friendship Qualities
Scale,” and “The Dimensions of Identity Development Scale.”
Two-stage structural equation modeling was employed to analyze the gathered data.
The findings indicated a positive model of identity development in adolescents,
highlighting that subjective well-being increasing strategies contribute positively
to identity development, and this relationship is mediated by positive body image.
Furthermore, the study found that positive body image also mediates the association
between adolescents’ identity development and the establishment of quality
friendships.
Filling data gaps in long-term solar UV monitoring by statistical imputation methods
Authors: Heinzl Felix , Lorenz Sebastian , Scholz-Kreisel Peter , Weiskopf Daniela
Published: May 2024

Knowledge of long-term time trends of solar ultraviolet (UV) radiation on ground level is of high scientific interest. For this purpose, precise measurements over a long time are necessary. One of the challenges solar UV monitoring faces is the permanent and gap-free data collection over several decades. Data gaps hamper the formation and comparison of monthly or annual means, and, in the worst case, lead to incorrect conclusions in further data evaluation and trend analysis of UV data. For estimating data to fill gaps in long-term UV data series (daily radiant exposure and highest daily irradiance), we developed three statistical imputation methods: a model-based imputation, considering actual local solar radiation conditions using predictors correlated to the local UV values in an empirical model; an average-based imputation based on a statistical approach of averaging available local UV measurement data without predictors; and a mixture of these two imputation methods. A detailed validation demonstrates the superiority of the model-based imputation method. The combined method can be considered the best one in practice. Furthermore, it has been shown that the model-based imputation method can be used as an useful tool to identify systematic errors at and between calibration steps in long-term erythemal UV data series.
X-ray screening of donated wild game is insufficient to protect children from lead exposure
Authors: Buenz Eric J. , Parry Gareth J. , Hunter Simon , Powell Garret M. , Berghamer Dominik , Cieraad Ellen , Hampton Jordan O. , Arnemo Jon M. , Bauer Brent A.
Published: May 2024

Worldwide hunters distribute game meat as a gesture of community bonding and as an essential nutritional resource for those facing food insecurity, especially among children and adolescents. Nonetheless, the risk of lead (Pb) contamination from lead-based bullets is not widely acknowledged. Although medical radiography (X-ray) is the standard method to detect lead in meat donations, its efficacy in conclusively identifying lead contamination in game meat samples remains unknown. To address this deficiency, hunters-provided game meat samples were analyzed using both X-ray and inductively-coupled plasma mass spectrometry (ICP-MS). By ICP-MS, 48% of these samples contained lead levels exceeding the daily intake benchmarks for children, including the samples in which no lead was identified by X-ray screening. This finding means that food insecure individuals need to make an unenviable decision between risking lead exposure in donated meat or forgoing a potentially critical food source.
Mathematics for Economics and Finance
Authors: Anthony Martin , Biggs Norman
Published: May 2024

Accessible, concise, and interactive, this book introduces the mathematical methods that are indispensable in economics and finance. Fully updated to be as student friendly as possible, this edition contains extensive problems, worked examples and exercises (with full solutions at the end of the book). Two brand new chapters cover coupled systems of recurrence/differential equations, and matrix diagonalisation. All topics are motivated by problems from economics and finance, demonstrating to students how they can apply the mathematical techniques covered. For undergraduate students of economics, mathematics, or both, this book will be welcomed for its clarity and breadth and the many opportunities it provides for readers to practise and test their understanding.
F.6 Opportunities for improvement: understanding drivers of emergency department visits within 90 days of posterior spinal decompression surgery
Authors: Smith-Forrester J , Douglas J , Nemeth E , Alant J , Barry S , Glennie A , Oxner W , Weise L , Christie S
Published: May 2024

Background: Canadian Emergency Departments (EDs) are overburdened. Understanding the drivers for postoperative patients to attend the ED allows for targeted interventions thereby reducing demand. We sought to identify “bounce back” patterns for subsequent QI initiatives. Methods: From April 1, 2016 to March 31, 2022, all provincial ED datasets (EDIS, STAR, Meditech) identified patients presenting within 90 days post-spine surgery. Using Canadian Classification of Health Interventions codes, laminectomies (1SC80) and discectomies (1SE87) demonstrated the highest ED visit rates. Comprehensive chart reviews were conducted identifying surgical and medical reasons for presentation within this timeframe. Results: Reviewing a cohort of 2165 post-decompression patients, 42.1% presented to the ED (n=912) with 62.8% of these directly related to surgery. Primary reasons included wound care (31.6%), pain management (31.6%), and bladder issues (retention or UTI, 11.0%). Simple wound evaluation constituted 49.7% of wound-related visits, with surgical site infection 37.6% and dehiscence 6.6% accounting for the remainder. Pain-related presentations resulted in 72.3% discharge with additional medications, and 27.7% necessitating hospital admission. New or worsening neurologic deficits were reported in 8.9% of ED visits. Conclusions: These findings illuminate crucial aspects of postoperative care and ED utilization patterns. Prioritizing patient education, pain management, and wound care could help alleviate the national ED crisis.
P.028 Exploring young adult stroke patients’ lived experience, healthy lifestyle habits, and recommendations for designing innovative brain care-related initiatives
Authors: Ibrahim S , Hashmi S , D’Amico D , Verven A , Zhang L , Ng S , Casaubon LK , Sivakumar K , Pikula A
Published: May 2024

Background: Over the past decade, worldwide stroke incidence has been increasing among young adults (≤65years), which has implications during the most dynamic period of their life. There is a dearth of research exploring young adults stroke patients’ experiences, healthy lifestyle habits, preferences, and recommendations for brain care-related initiatives. The study aimed to gain knowledge and a deeper understanding of young adult stroke patients’ experiences, lifestyle habits, and support needs for brain care-related education and interventions. Methods: A descriptive qualitative study was used. Participants who took part in the quantitative phase of a larger mixed methods study (n=103 that expressed an interest in the qualitative phase, were invited to take part in semi-structured focus groups. Simultaneous data collection and analysis are being conducted. Data are being analyzed using inductive thematic analysis outlined by Braun and Clarke (2006). Results: Findings will be available by May 20, 2024. Conclusions: Study findings will be essential to 1) mobilize an understanding of young adult stroke patients’ lived experience; 2) reconceptualize the current model of stroke care and services that is traditionally geared towards older adults; and 3) inform the development of brain care-related education and interventions to meet the unique needs, priorities, and preferences of young adult stroke patients.
P.043 Developing a brief clinical dataset for Duchenne Muscular Dystrophy
Authors: Bourcier D , Hodgkinson V , Dyck A , Drisdelle S , Korngut L , Sheriko J
Published: May 2024

Background: Duchenne muscular dystrophy (DMD) causes progressive muscle wasting. The Canadian Neuromuscular Disease Registry (CNDR) previously developed a comprehensive DMD dataset in accordance with the International Classification of Functioning, Disability, and Health (ICF). Our objective was to develop a brief ICF core set that best aligns with the priorities of individuals and families affected by DMD. Methods: A literature review of best practices was prepared and reviewed by a multidisciplinary team at the CNDR. The entire process involved patient and parent input and participation and was compliant with the World Health Organization guideline to develop brief ICF core sets. Results: An eight step process was developed. In brief, these included multi-stakeholder consensus meetings, ranking surveys, mapping to international standards, further consensus meeting, evaluation of clinical feasibility in multidisciplinary clinics across Canada, an integrated literature review, and development of a finalized brief ICF core set for DMD. Conclusions: The process of identifying the priorities of those living with DMD using the brief ICF core set will support post-marketing surveillance of novel therapies. The next step in this project will be to identify the specific outcome measures that best align with the brief ICF core set for DMD, for their eventual inclusion in the CNDR registry.
P.055 Corticosteroid dose tapering in patients with generalised myasthenia gravis on zilucoplan: Interim analysis of RAISE-XT
Authors: Genge A , Hewamadduma C , Freimer M , Leite MI , Beau Lejdstrom R , Boroojerdi B , Grimson F , Savic N , Howard JF
Published: May 2024

Background: In the Phase 3 RAISE study (NCT04115293), zilucoplan significantly improved MG-specific outcomes in patients with acetylcholine receptor autoantibody-positive generalised MG. After the first 12 weeks of the open-label extension study, RAISE-XT (NCT04225871), corticosteroid dose could be changed per the investigator’s discretion. We evaluate changes in corticosteroid dose during treatment with zilucoplan in RAISE-XT. Methods: In RAISE-XT, adults who completed the Phase 2 or RAISE studies (N=200) self-administered daily subcutaneous zilucoplan 0.3mg/kg, either continuing with zilucoplan or switching from placebo. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). We assessed (post-hoc) the proportion of patients who discontinued/reduced or increased corticosteroid dose relative to double-blind baseline up to Week 60. Results: At Week 60, 30% (n=18/60) and 22% (n=12/54) of patients receiving corticosteroids in the zilucoplan and placebo-switch groups, respectively, reduced/discontinued corticosteroids (mean dose reductions: 14mg and 16mg; mean [SD] CFB in MG-ADL scores: -5.00 [3.96] and -5.67 [6.89]. 12% (n=7/60) and 7% (n=4/54) of patients in the zilucoplan and placebo-switch groups, respectively, increased corticosteroid dose (~12mg mean increase in both groups). TEAEs occurred in 188 (94.0%) patients (data cut-off: 08 September 2022). Conclusions: While receiving zilucoplan, discontinuation or dose reduction in concomitant corticosteroids was possible with maintained efficacy.
P.058 Neuromuscular neurologists’ experience in recognizing, diagnosing, and treating Long-chain fatty acid disorders (LC-FAOD): a national survey
Authors: Kassardjian CD , Dyck A , Andrews S , Schellenberg K , McMillan H , Hodgkinson V , Korngut L
Published: May 2024

Background: LC-FAOD may be missed in neuromuscular (NM) clinics due to its rarity and absence from common NM genetic panels. The Canadian Neuromuscular Disease Registry (CNDR) collects real-world patient data and includes a network of clinician-investigators. Our objective was to inform future registry work by evaluating diagnosis pathways for LC-FAOD patients and estimating the number followed at Canadian NM clinics. Methods: A questionnaire was developed with an expert committee and circulated to 111 CNDR-affiliated NM neurologists. Results: 12 neurologists in 5 provinces, primarily adult-treating (n=8) completed the survey (10.8% response rate). Eleven (91.7%) practiced for >10 years. Agreement trends existed between definition of, and tests to evaluate, rhabdomyolysis. Four clinics routinely follow LC-FAOD patients. In the last 1-2 years, respondents diagnosed approximately 91 patients with LC-FAOD (mean=7.5 per clinic). 83.3% never received continuing education on LC-FAOD, though 75% indicated interest in expert-led webinars. Further data will be presented. Conclusions: Low sample size limits conclusions about LC-FAOD clinical trends. Results suggest LC-FAOD may be under-diagnosed or not routinely followed by NM specialists, limiting viability of an LC-FAOD registry. Practitioners may be interested in LC-FAOD-specific education. Future work could include collaboration with metabolic geneticists on education initiatives to raise awareness and improve care for these patients.
P.068 Malignant transformation of a spinal dermoid cyst into carcinosarcoma
Authors: Chaiton JA
Published: May 2024

Background: Spinal dermoid cysts are uncommon, benign tumours of ectodermal origin, often associated with spinal dysraphism. Malignant transformation of spinal dermoid cysts is an exceptionally rare entity, with transformation into carcinosarcoma not previously reported. Methods: Case report and literature review Results: A 41-year-old male presented with a recurrent lumbar intradural mass, 28 years after resection of a dermal sinus tract and associated dermoid cyst. Intraoperative appearance and subsequent pathology were again consistent with a dermoid cyst. The patient re-presented 2 weeks after surgery with diplopia and headache due to hydrocephalus, thought to be due to chemical meningitis. Following ventriculoperitoneal shunt implantation, the patient rapidly deteriorated with progressive neurologic deficits and widespread leptomeningeal enhancement. A repeat spinal leptomeningeal biopsy was pursued, which revealed malignant transformation of the dermoid cyst into invasive carcinosarcoma. Without curative treatment options, the patient was palliated and died 85 days after admission. Conclusions: Malignant transformation of spinal dermoid cysts should be considered in the differential diagnosis of patients with dermoid cysts and progressive leptomeningeal enhancement. False negatives can occur with initial tumour pathology and repeat sampling may be warranted for diagnostic clarity. To the authors knowledge, this is the first report of a spinal dermoid cyst with malignant transformation into carcinosarcoma.
P.074 Assessing the emergence and evolution of artificial intelligence and machine learning research in neuroradiology
Authors: Haile SS , Boutet A , Wang AZ , Son H , Malik M , Pai V , Nasralla M , Germann J , Vetkas A , Khalvati F , Ertl-Wagner BB
Published: May 2024

Background: Interest in artificial intelligence (AI) and machine learning (ML) has been growing in neuroradiology, but there is limited knowledge on how this interest has manifested into research and the field’s trends, challenges, and future directions. Methods: The American Journal of Neuroradiology was queried for original research articles published since inception (Jan. 1, 1980) to Sept. 19, 2022 that contained any of the following key terms: “machine learning”, “artificial intelligence”, or “radiomics”. Articles were screened, categorized into Statistical Modelling (Type 1), AI/ML Development (Type 2), or End-user Application (Type 3) and then bibliometrically analyzed. Results: A total of 124 articles were identified with 85% being non-integration focused (Type 1 n = 41, Type 2 n = 65) and the remaining (n = 18) being Type 3. The total number of articles published grew two-fold in the last five years, with Type 2 articles mainly driving this growth. While most (66%) Type 2 articles were led by a radiologist with 55% possessing a postgraduate degree, a minority of Type 2 articles addressed bias (15%) and explainability (20%). Conclusions: The results of this study highlight areas for improvement but also strengths that stakeholders can consider when promoting the shift towards integrating practical AI/ML solutions in neuroradiology.
P.077 Reducing artifact during in bi-directional brain interfacing
Authors: Tourigny K , Denison T
Published: May 2024

Background: Bi-directional brain interfacing (closed loop DBS) is a modern focus of neuroengineering research. Most current clinical systems are open loop, allowing one way communication from the IPG battery to the brain. Bi-directional systems allow both stimulation and recording of neural activity (local field potential, LFP). The system algorithm can measure known pathologic LFPs to guide change in stimulation. However, recording LFPs from the brain encounters electrical artifact from the heart. Reducing artifact is imperative to accurate measurement of neural activity. Artifact will cause the bi-directional system to miscalculate stimulation parameters. This project evaluated reduction of artifact by moving the IPG further away from the heart in a device implanted into the skull. Methods: LFP data from ongoing clinical trials was collected and analysed for artifact using open source code. Anatomic targets include STN, PPN, CMT, and PAG. Results: Cardiac artifact is reduced in skull mounted DBS as shown by power spectral density of LFPs in each region. Conclusions: This project shows the importance of surgical placement of DBS sensing devices to reduce cardiac artifact in bi-directional brain interfacing. This has important engineering and surgical design implications for safety and performance as the field of closed loop DBS transitions from research to clinical settings.
P.105 Corpus callosum changes in children affected by infantile hydrocephalus
Authors: Adil D , Duerden E , Eagleson R , de Ribaupierre S
Published: May 2024

Background: Infantile hydrocephalus is characterized by an atypical accumulation of cerebrospinal fluid in the brain, diagnosed and treated before the age of 2 years. Hydrocephalus development is linked to thinning of the corpus callosum (CC), mainly due to the expansion of lateral ventricles, causing upward elevation and compression of periventricular and subcortical white matter. Methods: This study investigates structural alterations in the CC in children diagnosed with infantile hydrocephalus. We examined both macrostructural and microstructural facets of the CC, providing insights into the nature and extent of alterations associated with this condition. 18 patients with infantile hydrocephalus (mean age = 9 years), and 18 age and sex matched typically-developing healthy children, participated in the study. Structural magnetic resonance imaging and diffusion tensor imaging were utilized to assess CC volume and microstructure, respectively. Results: Our findings reveal reductions in CC volume, particularly in posterior area, and distinct microstructural disparities, notably pronounced in these same segments. Conclusions: Investigating these structural alterations provides an understanding into the mechanisms underlying the effects of infantile hydrocephalus on CC integrity, given its role as a neural bridge. This knowledge offers a more nuanced perspective on neurological disorders and underscores the significance of investigating the CC’s health in such contexts.
P.128 Pituitary apoplexy: a retrospective single center cohort study
Authors: Parker E , Imran SA , Hebb A , Kureshi N , Clarke DB
Published: May 2024

Background: Pituitary apoplexy is a rare clinical syndrome resulting from infarction or hemorrhage of a pituitary tumor. Here, we present a large single center retrospective cohort study of patients with apoplexy. Methods: Patients with symptomatic apoplexy treated from January 2000 to October 2022 were isolated from the Halifax Neuropituitary Program’s database, containing prospectively entered data. Patients treated surgically typically presented with vision deterioration or decreased consciousness. Patient demographics, tumor size, endocrinologic values, and clinical outcomes were analyzed. Results: Eighty-three patients met our inclusion criteria. Seventy-two percent of tumours (n=60) were biochemically non-functioning adenomas. Sixty (72.3%) patients were treated surgically, while twenty-three (27.7%) were treated conservatively. At time of presentation, patients treated surgically had a tumor size in maximum dimension of 2.7±1.4 cm versus 1.6±0.5 cm for those treated conservatively (p=0.0003). There were no significant differences in endocrinological values at time of presentation between groups. Fifteen percent (n=9) of patients treated surgically underwent an additional surgery (mean 2.8±2.0 years from index), of which 67% (n=6) were secondary to tumor recurrence. Conclusions: This is one of the largest reported series of apoplexy with long-term follow up. A subset of surgically treated patients will require additional intervention, highlighting the importance of ongoing follow up in this population.