bluuebunny/crossref_metadata_2025 huggingface dataset:
P.112 Understanding obstacles: a neurosurgical view on gender disparities in career progression
Authors: Istasy MV , Shitsama S , Skulsampaopol J , Cusimano MD
Published: May 2024

Background: Gender disparities persist in neurosurgery, unfortunately impacting career progression for women. Understanding these challenges is vital for fostering inclusivity. Methods: An international survey designed using a physician wellness framework was sent to neurosurgeons between June 2021 and November 2021. Univariate analysis (Kruskal-Wallis Test) was performed to assess various aspects of perceived career progression as a function of gender. Results: Of the total 537 respondents (64% neurosurgeons, 6% fellows, and 30% residents), 69% identified as male, 29% as female, and 2% as other. Compared to their male colleagues, female neurosurgeons expressed greater desire to advance in their career (p<0.05) and to leave their home country in the interest of job prospects (p<0.05). Despite these aspirations, female neurosurgeons reported that they did not have available career advancement opportunities (p<0.05), that the culture in their country inhibited their career advancement (p<0.05), and that they felt subject to harassment at their workplace (p<0.05). Conclusions: Our survey highlights significant gender-related obstacles in neurosurgical career advancement. Female neurosurgeons express strong career aspirations but face barriers such as limited opportunities, cultural impediments, and harassment. Addressing these challenges is crucial for achieving gender equity in neurosurgery.
P.113 Mind the gap: illuminating gender disparities in neurosurgical inclusion and diversity
Authors: Istasy MV , Shitsama S , Skulsampaopol J , Cusimano MD
Published: May 2024

Background: Gender disparities endure in neurosurgery, impacting the experiences of female practitioners. Unveiling these challenges is crucial for promoting inclusivity and addressing the unique obstacles faced by women in the field. Methods: An international survey designed using a physician wellness framework was sent to neurosurgeons between June 2021 and November 2021. Univariate analysis (Kruskal-Wallis Test) was performed to assess feelings of inclusion and diversity as a function of gender. Results: Of the total 384 respondents (65% neurosurgeons, 6% fellows, and 29% residents), 71% identified as male, 27% as female, and 2% as other. Compared to their male colleagues, female neurosurgeons more strongly endorsed feeling that their career progression has been limited by their gender (p<0.05) and were less likely to feel entrusted in their surgical ability (p<0.05) or to have equal access to surgical resources (p<0.05). Furthermore, they were less likely to endorse feelings that leaders in their department were committed to creating an inclusive environment (p<0.05). Conclusions: Our survey sheds light on significant gender-related disparities in neurosurgery. Female neurosurgeons express heightened concerns about gender-limiting career progression, reduced trust in their surgical abilities, and disparities in resource access. These findings underscore the imperative to foster a more inclusive and supportive environment within the field.
P.115 The national impact of traumatic brain injury on labor markets: a canada-wide observational cohort study of post-injury employment and personal income loss
Authors: Malhotra AK , Jaffe RH , Shakil H , Mathieu F , Nathens AB , Kulkarni AV , Diep C , Ladha KS , Wilson JR , Witiw CD
Published: May 2024

Background: Employment and personal income loss after traumatic brain injury (TBI) is a major source of post-injury stress and barrier to societal reintegration for affected patients. We sought to quantify the labor market implications for tax-filing adult TBI survivors. Methods: We performed a matched difference-in-difference analysis using a national retrospective cohort of working adult TBI survivors injured between 2007-2017. Linear and logistic mixed effects regressions were used to estimate the magnitude of personal income loss and proportion of patients displaced from the workforce in the three post-injury years (Y+1 to Y+3). Results: Among 18,050 patients identified with TBI, the adjusted average loss of personal annual income was $-7,635 dollars in Y+1 and $-5,000 in Y+3. An additional -7.8% individuals were newly unemployed compared to the pre-injury baseline. For mild, moderate, and severe TBI subgroups, income loss was $-3354, $-6750, and $-17375 respectively in Y+3; the proportion of newly unemployed individuals in Y+3 was 5.8%, 9.2%, and 20% lower than baseline. We estimated 500 million dollars of incurred labor markets losses related to TBI in Canada. Conclusions: This work represents the first national cohort data quantifying the labor market implications of TBI. These results may be used to inform post-injury care pathways and vocational rehabilitation.
P.117 Antiplatelet and anticoagulation use and outcomes following chronic subdural hematoma drainage: systematic review and meta-analysis
Authors: Liu E , Zhou A , Tilbury N , Su J , Persad AR , Radic J
Published: May 2024

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical condition which can be treated with surgical evacuation. A significant percentage of CSDH patients are on antiplatelet or anticoagulation therapy at baseline which may influence risk of recurrence and postoperative thromboembolic events Methods: A search was conducted in MEDLINE (1946 to April 6, 2023), Embase (1974 to April 6, 2023), and PubMed (up to April 6, 2023) on preoperative use of antiplatelet or anticoagulation therapy and outcomes following surgical evacuation of CSDH. Results: Our literature includes 14,410 patients ifrom 42 studies, with 3218 (22%) in the antiplatelet (AP) group, 1731(12%) in the anticoagulation (AC) group, and 9537 (66%) in the no antithrombotics (NA) group. The AP group had significantly higher recurrence compared to NA (OR = 1.21, 95% CI = 1.04 to 1.40, p = 0.01). The AC group also had significantly high recurrence compared to NA (OR = 1.39. 95% CI = 1.15 to 1.68, p = 0.0007). However, being on any antithrombotic therapy is also associated with significantly higher thromboembolic events (OR 5.41, 95% CI 3.16 to 9.26, p < 0.00001). Conclusions: Patients on antithrombotic therapy have both higher recurrence and higher thromboembolic risk compared to patients not on antithrombotic therapy.
P.119 NIRS regional oxygen saturation based cerebrovascular reactivity in the recovery from moderate/severe TBI
Authors: Gomez A , Froese L , Bergmann T , Sainbhi AS , Vakitbilir N , Islam A , Stein KY , Marquez I , Ibrahim Y , Zeiler FA
Published: May 2024

Background: Near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2) based cerebrovascular reactivity (CVR) indicies have enable the entirely non-invasive continuous monitoring. This study aims to compare CVR in those recovering from moderate/severe TBI to a health control group. Methods: In this prospective cohort study the cerebral oxygen CVR index, COx_a (using rSO2 and arterial blood pressure), was measured in subjects with moderate/severe TBI at follow-up. COx_a was also measured in a group of healthy controls. CVR was compared within and between these groups using conventional statistics. Results: A total of 101 heathy subject were recruited for this study along with 29 TBI patients. In the health cohort COx_a was not statistically different between males and females or in the dominate and non-dominate hemisphere. The TBI cohort, COx_a was not statistically different between first and last available follow up. Surprisingly, CVR as measured by COx_a was statistically better in those recovering from TBI than in the healthy cohort. Conclusions: In the prospective cohort study, CVR as measured by NIRS based methods, was found to be more active in those recovering from TBI than in a healthy cohort. This study may indicate that, in those that survive TBI, CVR may be enhanced as a neuroprotective measure.
P.121 Subgaleal versus subdural drain after minicraniotomy for chronic subdural haematoma
Authors: Kam J , Li S , Ho B , Akagami R , Rebchuk A , Wang J , Farsakh A , Lai L
Published: May 2024

Background: Subdural and subgaleal drains are equally effective after burrhole craniostomy for chronic subdural haematoma, however the optimal location of drains after minicraniotomy is not clear. As such we present the first study to assess this. Methods: Consecutive patients undergoing minicraniotomy for cSDH between 2019 and 2023 at a single institution were included. Subgaleal drains were placed exclusively by a single surgeon with the rest of the department utilising standard subdural drains. Cases were stratified by drain location. Primary outcomes included changes in functional status (Modified Rankin Score, mRS) at 3 months from preoperative baseline. Results: A total of 137 patients were included, of which 24.6% received subgaleal drains. Discharge home was higher in the subgaleal group compared to subdural group (79.4% vs 57.3%, p=0.02). Subgaleal drain location (p<0.0001) and better preoperative GCS (p=0.01) were predictors of improved 3 month mRS. Worse premorbid mRS (p=0.002), subdural drain (p=0.004), and decreased consciousness at presentation (p<0.002) were predictors of not being discharged home. Surgical recurrence was lower in the subgaleal group than the subdural group (2.9% vs 13.6%, p=0.12), but not statistically significant. Conclusions: Subgaleal drains are associated with shorter hospitalisation, greater chance of discharge home, and better functional outcomes than subdural drains.
P.122 Left temporal aneurysm resection: surgical approach in Pial-Pial collateral formation from the posterior temporal artery secondary to left internal artery occlusion
Authors: Pascual JS , Guo E , Yang R , Langdon KD , Lama S , Sutherland GR
Published: May 2024

Background: The formation of pial-pial collateral network aneurysms due to carotid occlusion is a rare neurological phenomenon. This case details a 69-year-old male who developed a pial-pial collateral network aneurysm secondary to left internal carotid artery occlusion, leading to intracranial hemorrhage. Methods: The patient presented with altered consciousness due to left temporal intracerebral hemorrhage, subdural hematoma, and intraventricular hemorrhage. Cerebral angiography revealed an occluded left internal carotid artery, with superficial temporal artery (STA) and superior orbital artery anastomosis, and extensive pial-pial collaterals from the posterior temporal artery. A 4 mm aneurysm arising from this collateral network was identified. Surgical intervention involved a left temporal craniectomy and excision of the aneurysm, prioritizing the preservation of the STA. N.B., Informed patient consent was obtained in this study. Results: Successful aneurysm removal and preservation of collateral pathways were confirmed by postoperative imaging. The patient exhibited rapid neurological improvement; by postoperative day (POD) one, the patient showed limited response to stimuli. He was extubated by POD4 and discharged on POD27, where he conversed well, was independently ambulatory, and needed minimal to no assistance in activities of daily living. Conclusions: This case highlights the need for careful preoperative planning and intraoperative precision, especially in preserving vital collateral vascular pathways.
P.125 Cerebral AVM recurrence post gamma knife obliteration: a 20 year single centre retrospective analysis and review of literature
Authors: Grajauskas LA , Patel S , Kaufmann A
Published: May 2024

Background: Pediatric arteriovenous malformations (AVMs) are rare, but represent the leading cause of intracranial hemorrhage in children. These are traditionally understood to be congenital lesions, however AVMs recurrence within previously unaffected tissue challenges this understanding. Recurrence after microsurgery and endovascular treatment have been studied in greater detail, but little literature exists surrounding recurrence after Gamma Knife Radiosurgery (GKRS). Methods: We performed a retrospective chart review of all pediatric AVMs treated with GKRS at our centre. Charts were assessed by two reviewers to identify cases of AVM recurrence after angiographically confirmed obliteration. To contextualize our institutional patterns, we also performed a structured literature review of published data reporting pediatric AVM recurrence after GKRS. Results: Our institutional review revealed two cases of AVM recurrence after angiographically proven cure, and our review of literature identified nine retrospective reviews and three case reports, which in total reported 22 individual cases of recurrence. The recurrence rate in the retrospective reviews ranged from 0 to 18%. Conclusions: The current work illustrates that while AVM recurrence is rare, it is a possible complication of GKRS. There was also a qualitative suggestion that embolization prior to CT increased risk of recurrence. Both these facts should be included in decision-making and patient counselling.
P.127 Quality of life (QoL) using EORTC QoL-C30 and BN20 among patients who underwent brain tumor resection in a tertiary hospital in Saudi Arabia
Authors: Moshref R , Moshref L , Sabbagh AJ , Bajunaid K , Alyousef M , Baeesa S , Daghistani R , Alhalawani FA , Aljehani MA , Shibriq NM , Saber WA , Khojah AB , Alsayed RM
Published: May 2024

Background: Quality of life (QoL) is the awareness of individuals’ well-being in life in physical, personal, mental and social wellbeing and needs to be addressed in brain tumor patients. Methods: A retrospective study conducted in 2017 in a single academic center that included patients diagnosed with brain tumors in a 10 year period. The assessment of the QoL was done using the European Organization for Research and Treatment of Cancer (EORTC), a standardized model (QLQ-C30) that assess several domains (Global Health, Physical function, Role functioning, Emotional Functioning, Cognitive functioning, social functioning and symptoms domain) and Brain cancer model (BN20) to assess symptoms to evaluate all aspects of wellbeing. Results: The total number of patients included in this study is 76 patients with no gender predilection. The most common brain tumor was meningioma by 40% followed by glioma/ others. More than half of the brain tumor patients had a WHO grade I (65%), intermediate grading grade II (15%) and higher grading grade III/IV (20%). The scales and measurements of functioning in life were low in all types of brain tumors. Conclusions: Quality of life in brain tumor patients seemed poor regardless of the type. Further prospective studies are needed to assess QoL worldwide.
P.129 Canadian neurosurgical healthcare spending trends
Authors: Guo E , Sanguinetti R , Boone L , Karmur BS , Lama S , Sutherland GR
Published: May 2024

Background: Neurosurgical conditions impose a significant burden on the Canadian healthcare system. This study quantifies the economic impact and explores predictive models for postoperative length of stay. Methods: We analyzed data from the Canadian Institute for Health Information National Health Expenditure Trends database for 2015-2019, focusing on case volumes, healthcare costs, and lengths of stay (LOS) across age groups and conditions. Decision tree models were created to predict total LOS from patient age and average acute LOS. Results: There was a modest increase in case volumes from 6,220 ± 3,103 in 2015 to 6,492 ± 3,240 in 2018, with a slight decrease in 2019. The total estimated hospital costs ranged from 2.27 ± 0.38 million CAD in 2015 to 2.23 ± 0.44 million CAD in 2019. The highest costs were seen in the 18-59 age group, at 2.53 ± 0.43 million CAD. Decision tree models showed high accuracy for predicting LOS in cases like spinal injury (F1-score: 0.98) but were less accurate for interventions with trauma or complications (F1-scores from 0.66 to 0.97). Conclusions: The study delineates the financial demands of neurosurgery in Canada and suggests decision tree models as useful tools for predicting hospital stay, with variable accuracy depending on the case complexity.
P.130 Endoscopic fenestration of trapped fourth ventricle
Authors: Libbus KM , Walling SA , Leck ED , McNeely PD
Published: May 2024

Background: Trapped fourth ventricle (TFV) is a rare entity that occurs when the fourth ventricle is obstructed and isolated from the normal cerebrospinal fluid (CSF) circulation. While not always symptomatic, TFV can lead to compression of the cerebellum and brainstem, with potential for serious consequences. Treatment of TFV can be challenging, with options including CSF diversion via shunts versus open or endoscopic fenestrations. In this report, we describe a case of TFV that was managed endoscopically. Methods: A seven-year-old girl with a history of myelomeningocele and hydrocephalus, presented with a change in neurological status. Imaging of the brain and spine showed syringomyelia, markedly dilated ventricles, and a TFV. An endoscopic approach was used to fenestrate the wall of the fourth ventricle. Results: While there was an early favorable outcome, the first fenestration closed over within one month, requiring a repeat endoscopic fenestration. Both procedures were complicated by transient seizures, requiring a pediatric intensive care unit (PICU) admission after the second intervention. Pre- and post-operative clinical and diagnostic imaging findings are reported. Conclusions: Endoscopic fenestration can be an effective treatment option for management of TFV. The patient, family, and treating team should be prepared to deal with acute peri-operative complications that may require PICU management.
P.134 Long-term quality of life deterioration in vestibular schwannoma patients treated with radiotherapy: a matched cohort with surveillance, radiation and surgery
Authors: Taniguchi S , Kam J , Akagami R
Published: May 2024

Background: There is an absence of studies evaluating longitudinal quality of life (QoL) amongst vestibular schwannomas (VS) with matched tumor and patient characteristics between treatment groups. We present novel findings of 12 yearlong follow-up of patient QoL and symptomatology outcomes in this matched cohort study. Methods: Symptomatology and 36-Item Short Form Health Survey (SF36) between 2000-2017 in VS patients managed at a single tertiary centre was conducted. Radiation (R) and active surveillance (A) groups were matched for tumor size and age against the surgery (S) group. Results: 14 A patients, 24 R patients, 49 S patients met matching and inclusion criteria. Mean age, tumor diameter and follow up was 69.1 years, 21.6mm and 12.0 years respectively. Mental component summary (MCS) scores deteriorated significantly in the radiation group (3.1 S, 3.7 A, -3.5 R, p-value 0.008). Physical component summary scores remained stable at follow up (-0.2 S, 0.00 S, -4.0 R, p-value 0.227). Various symptoms resolved statistically in surgery goup, whereas tinnitus on follow up was higher with radiation (40.8% S, 66.7% R, p-value 0.038). Conclusions: Surgery group demonstrated improvements in long term QoL with good symptom resolution, whilst radiation group demonstrated small but significant deterioration over time.
P.137 Neurosurgical consultations in Nova Scotia: a descriptive analysis
Authors: Parker E , MacLean MA , Leck E , Han J , Alwadei A , Greene R , Clarke DB
Published: May 2024

Background: Receiving and managing neurosurgical consultations are central to providing quality patient care but are resource intensive processes. As part of an ongoing quality improvement initiative, we conducted a single-institution descriptive analysis of adult neurosurgical consultations. Methods: A retrospective review of prospectively collected consultation records and call schedules from a 12-month period from February 2019 to 2020 was performed. Consults were graded according to disposition (admission for surgery, non-operative admission, additional investigations recommended, opinion without further investigations, unnecessary consult). Results: There were 1916 consultations reviewed, with 52% of calls (n=991) originating outside of our hospital, and 72% (n=1387) coming from an emergency department. Cranial cases made up 64% (n=1230) of consults, while the remaining 36% (n=688) were spine cases. The mean patient age was 60.1±0.4 years. In multinomial logistic regression analysis, age, geographical distance of consulting site, and consult specific variables (neurosurgical subspecialty, inside vs. outside call, emergency department vs. inpatient ward or private office) were associated with consult disposition (p < 0.001). Conclusions: This study provides a descriptive analysis of neurosurgical consultations in Nova Scotia. Results from this study may be used to address inefficacies in the neurosurgical consultation process, including targeted education for consulting physicians.
P.139 The use of tranexamic acid in craniotomy: a Canadian survey and literature review
Authors: Jung S , Julien L , Christie SD , Lownie SP
Published: May 2024

Background: There is growing evidence supporting the intraoperative use of an antifibrinolytic agent, tranexamic acid (TXA) to limit blood loss; however, use of TXA has not been widely adopted in cranial procedures. We aimed to determine the practice pattern regarding the use of TXA in craniotomy in Canada, and review the literature. Methods: A survey was conducted among the Canadian centres on TXA use during elective craniotomy. Online databases were searched for randomized controlled trials reporting the use of TXA in craniotomy for tumors. The results included the estimated blood loss and the dose used. Results: TXA was not routinely used in elective craniotomy but used selectively in 6 of 15 centres based on risk, intraoperative bleeding, or surgeon preference. The dose was 1 g with or without infusion. 6 studies were identified through literature search. The dose varied between 10–20 mg/kg bolus and 1 mg/kg/hr infusion, or a 2 g bolus alone. All studies reported a significant reduction in blood loss with TXA. Conclusions: We found widely divergent indications for intraoperative TXA use in elective craniotomy throughout Canada. This is in keeping with limited evidence in the literature. Further studies are needed to inform the decision regarding TXA use.
P.141 Endoscopic transorbital approach to the skull base: a single centre experience
Authors: Yasuda ME , Moore J , Nguyen T , Alammar Y , Mohd Slim MA , Mastrolonardo A , Sommer D , Reddy K
Published: May 2024

Background: Minimally invasive endoscopic techniques via the transorbital approach (ETOA) have emerged as a promising alternative for addressing skull base tumours. This study aims to showcase our institution’s extensive experience with ETOA, detailing the surgical technique employed and presenting comprehensive patient outcomes. Methods: A retrospective analysis was conducted on data from patients who underwent ETOA within the past five years. Results: Over the study period, 24 ETOA procedures were performed on 21 patients, with an average age of 48.92, 13 of whom were women. The superior orbital corridor was utilized in 95.83% of cases, and in 79.17%, ETOA was complemented by a transnasal approach. Spheno-orbital meningioma accounted for the most common surgical indication (33.33%, n=8), all resulting in vision improvement, followed by lateral frontal sinus mucocele (25%, n=6). The median length of stay was one day, and ETOA achieved the procedure goal in 19 patients. Transient V1 numbness was the primary complication (29.17%, n=7), and 20.83% (n=5) necessitated another surgery. Notably, no mortality was associated with this procedure. Conclusions: Our institution’s experience underscores the notable safety and efficacy potential of ETOA, with 19 out of 21 patients exhibiting positive outcomes, obviating the need for revision surgery in most cases.
GR.3 Distinct longitudinal brain atrophy trajectories in parkinson’s disease clinical subtypes: insight towards precision medicine
Authors: Fereshtehnejad S , Moqadam R , Postuma R , Dadar M , Lang A , Zeighami Y
Published: May 2024

Background: Parkinson’s disease (PD) varies widely across individuals in terms of clinical manifestations and course of progression. We aimed to compare patterns of brain atrophy between PD clinical subtypes using longitudinally acquired brain MRIs. Methods: We used T1-weighted MRIs from Parkinson’s Progression Markers Initiative (PPMI) on 134 PD individuals and 60 healthy controls with at least two MRIs. Patients were classified into three clinical subtypes at de novo stage using validated subtyping criteria based on major motor and non-motor classifiers (early cognitive impairment, RBD, dysautonomia): mild-motor predominant (n=74), intermediate (n=44), and diffuse-malignant (n=16). Deformation-based morphometry (DBM) maps were calculated and mixed effect models were used to examine the interaction between PD subtypes and rate of atrophy across brain regions over time, controlling for sex and age at baseline. Results: Individuals with ‘diffuse malignant’ PD showed a significantly higher rate of atrophy across multiple brain regions, including lateral nucleus of the forebrain, precuneus, paracentral lobule, inferior temporal gyrus, fusiform gyrus, and lateral hemisphere of the cerebellum (FDR corrected p<0.05). Conclusions: We demonstrated an accelerated atrophy pattern within several brain regions in ‘diffuse malignant’ PD subtype. These findings suggest the presence of a more diffuse multidomain neurodegenerative process in a subgroup of people with PD, favoring the existence of diverse underlying pathophysiologies.
GR.5 Establishing the utility of multi-platform liquid biopsy by integrating the CSF methylome and proteome in CNS malignancy
Authors: Landry AP , Zuccato JA , Patil V , Voisin M , Wang JZ , Ellenbogen Y , Gui C , Ajisebutu A , Nassiri F , Zadeh G
Published: May 2024

Background: Liquid biopsy represents a major development in cancer research, with significant translational potential. Similarly, the integration of multiple molecular platforms has yielded novel insights into disease biology and heterogeneity. We hypothesise that applying contemporary multi-omic approaches to liquid biopsies will improve the power of current models. Methods: We have compiled a cohort of 51 patients with glioblastoma, brain metastasis, and primary CNS lymphoma who underwent CSF sampling as part of clinical care. Cell free methylated DNA and shotgun proteomic profiling was obtained from the CSF of each patient and used to build tumour-specific classifiers. Integrated classifiers were compared with single platform classifiers using multiple approaches. Results: In this study, we show that the DNA methylation and protein profiles of cerebrospinal fluid can be combined to fully discriminate lymphomas from their major diagnostic counterparts with perfect AUCs of 1 (95% confidence interval 1-1) and 100% specificity. Each integrated lymphoma classifier significantly outperforms single-platform classifiers, suggesting synergistic biology is obtained using multiple molecular platforms. Conclusions: We present the most specific and accurate CNS lymphoma classifier to date by integrating the methylome and proteome of CSF. This has important implications for the future of cancer diagnostics and generates immediate utility for patients with CNS lymphoma.
A.1 Repurposing Ambroxol as a disease-modifying treatment for Parkinson’s disease dementia: A phase 2, randomized, double blind placebo-controlled trial
Authors: Pasternak SH , Silveira C , Coleman K , Borrie M , Wells J , Finger E , Bartha R , Jog M , Jenkins M , MacDonald P , Zou G , Stukas S , Wellington C , Tirona R , Rupar T
Published: May 2024

Background: Currently there are no disease modifying treatment for Synucleinopathies including Parkinson’s disease Dementia (PDD). Carrying a mutation in the GBA gene (beta-glucocerebrosidase/ GCAse) is a leading risk factor for synucleinopathies. Raising activity GCAse lowers α-synuclein levels in cells and animal models. Ambroxol is a pharmacological chaperone for GCAse and can raise GCAse levels. Our goal is to test Ambroxol as a disease-modifying treatment in PDD. Methods: We randomized fifty-five individuals with PDD to Ambroxol 1050mg/day, 525mg/day, or placebo for 52 weeks. Primary outcome measures included safety, Alzheimer’s disease Assessment Scale-cognitive (ADAS-Cog) subscale and the Clinician’s Global Impression of Change (CGIC). Secondary outcomes included pharmacokinetics, cognitive and motor outcomes and and plasma and CSF biomarkers. Results: Ambroxol was well tolerated. There were 7 serious adverse events (SAEs) none deemed related to Ambroxol. GCase activity was increased in white blood cells by ~1.5 fold. There were no differences between groups on primary outcome measures. Patients receiving high dose Ambroxol appeared better on the Neuropsychiatric Inventory. GBA carriers appeared to improve on some cognitive tests. pTau 181 was reduced in CSF. Conclusions: Ambroxol was safe and well-tolerated in PDD. Ambroxol may improve biomarkers and cognitive outcomes in GBA1 mutation carrie.rs Ambroxol improved some biomarkerss. ClinicalTrials.gov NCT02914366
A.3 Beta-amyloid is a cytokine and Alzheimer’s is an autoimmune disease
Authors: Weaver DF , Meek A , Reed M , Barden C
Published: May 2024

Background: Despite the limited successes of recent amyloid-targetting biologics, the need for a new pathogenesis mechanistic model of Alzheimer’s disease (AD) is a continuing priority, to facilitate improved rational drug design. Methods: To devise a new AD model, we performed an extensive, comprehensive series of in silico, in vitro, and in vivo studies explicitly evaluating the atomistic–molecular mechanisms of cytokine-mediated and amyloid-beta (Aβ)-mediated neurotoxicities in AD. Results: A new model of AD has been devised: In response to pathogen-/damage-associated molecular pattern-stimulating events (e.g., infection, trauma, ischaemia), Aβ is released as an early responder cytokine triggering an innate immunity cascade in which Aβ exhibits immunomodulatory/antimicrobial duality. However, Aβ’s antimicrobial properties result in a misdirected cytotoxic attack upon “self” neurons, arising from the electrophysiological similarities between neurons and bacteria in terms of transmembrane potential and anionic charges on outer membrane macromolecules. The subsequent breakdown products (amyloid-ganglioside complexes) released from the damaged neurons diffuse to adjacent neurons eliciting further release of Aβ, leading to a chronic, self-perpetuating disease cycle. In short, AD occurs because Aβ cannot differentiate neurons from bacteria. Conclusions: An innovative new model of AD has been devised, recognizing Aβ as a physiologically oligomerizing cytokine and conceptualizing AD as brain-centric autoimmune disorder of innate immunity.
A.6 INDIGO: a global, randomized, double-blinded, Phase 3 study of vorasidenib versus placebo in patients with grade 2 glioma with an IDH1/2 mutation (mIDH1/2)
Authors: Perry JR , Mellinghoff IK , van den Bent M , Blumenthal DT , Touat M , Peters KB , Clarke J , Mendez J , Yust-Katz S , Mason W , Ducray F , Umemura Y , Nabors B , Holdhoff M , Hottinger AF , Arakawa Y , Sepúlveda J , Wick W , Soffietti R , Giglio P , de la Fuente M , Maher E , Ellingson BM , Bottomley A , Zhao D , Pandya SS , Tron AE , Steelman L , Hassan I , Wen PY , Cloughesy TF
Published: May 2024

Background: We evaluated vorasidenib (VOR), a dual inhibitor of mIDH1/2, in patients with mIDH1/2 glioma (Phase 3; NCT04164901). Methods: Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (age ≥12; Karnofsky Performance Score ≥80; measurable non-enhancing disease; surgery as only prior treatment; not in immediate need of chemoradiotherapy). Patients were stratified by 1p19q status and baseline tumor size and randomized 1:1 to VOR 40 mg or placebo (PBO) daily in 28-day cycles. Endpoints included imaging-based progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), health-related quality of life (HRQoL), neurocognition and seizure activity. Results: 331 patients were randomized (VOR, 168; PBO, 163). The median age was 40.0 years. 172 and 159 patients had histologically confirmed oligodendroglioma and astrocytoma, respectively. Treatment with VOR significantly improved PFS and TTNI. Median PFS: VOR, 27.7 mos; PBO, 11.1 mos (P=0.000000067). Median TTNI: VOR, not reached; PBO, 17.8 mos (P=0.000000019). Treatment with VOR resulted in shrinkage of tumor volume. Post-treatment TGR: VOR, -2.5% (95% CI: -4.7, -0.2); PBO, 13.9% (95% CI: 11.1, 16.8). HRQoL and neurocognition were preserved and seizure control was maintained. VOR had a manageable safety profile. Conclusions: VOR was effective in mIDH1/2 diffuse glioma not in immediate need of chemoradiotherapy.
B.2 Time from symptom onset and number of health care encounters prior to diagnosis of cerebral venous thrombosis
Authors: Field T , Zhou LW , Dizonno V , Almekhlafi M , Bala F , Graham B , Sposato LA , Mandzia J , Medvedev G , Buck B , Boulos MI , Tkach A , Pikula A , Blacquiere D , Perera K , Odier C , Hill MD
Published: May 2024

Background: Cerebral venous thrombosis (CVT)most commonly affects younger women. Diagnosis may be delayed due to its distinct presentation and demographic profile compared to other stroke types. Methods: We examined delays to diagnosis of CVT in the SECRET randomized trial and TOP-SECRET parallel registry. Adults diagnosed with symptomatic CVT within <14 days were included. We examined time to diagnosis and number of health care encounters prior to diagnosis and associations with demographics, clinical and radiologic features and functional and patient-reported outcomes (PROMS) at days 180&365. Results: Of 103 participants, 68.9% were female; median age was 45 (IQR 31.0-61.0). Median time from symptom onset to diagnosis was 4 (1-8) days. Diagnosis on first presentation to medical attention was made in 60.2%. The difference in time to diagnosis for single versus multiple presentations was on the order of days (3[1-7] vs. 5[2-11.75], p=0.16). Women were likelier to have multiple presentations (OR 2.53; 95% CI1.00-6.39; p=0.05) and longer median times to diagnosis (5[2-8]days vs. 2[1-4.5] days; p=0.005). However, this was not associated with absolute or change in functional, or any patient reported, outcome measures (PROMs) at days 180&365. Conclusions: Diagnosis of CVT was commonly delayed; women were likelier to have multiple presentations. We found no association between delayed diagnosis and outcomes.
B.6 Long-term risk of subsequent stroke after transient ischemic attack or minor stroke: a systematic review and meta-analysis
Authors: Khan F , Yogendrakumar V , Lun R , Ganesh A , Lioutas V , Vinding N , Algra A , Weimar C , Ögren J , Edwards J , Swartz R , Ois A , Giralt-Steinhauer E , Bae H , Kamouchi M , de Leeuw F , Verhoeven J , Uehara T , Minematsu K , Fandler-Höfler S , Foschi M , Whiteley W , Purroy F , Jing J , Wang Y , Baik M , Kim Y , Spampinato M , Ildstad F , Hasegawa Y , Perera K , Park H , Dutta D , Barber P , Coutts S , Hill M
Published: May 2024

Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of subsequent stroke is uncertain. Methods: Electronic databases were searched for observational studies reporting subsequent stroke during a minimum follow-up of 1 year in patients with TIA or minor stroke. Unpublished data on number of stroke events and exact person-time at risk contributed by all patients during discrete time intervals of follow-up were requested from the authors of included studies. This information was used to calculate the incidence of stroke in individual studies, and results across studies were pooled using random-effects meta-analysis. Results: Fifteen independent cohorts involving 129794 patients were included in the analysis. The pooled incidence rate of subsequent stroke per 100 person-years was 6.4 events in the first year and 2.0 events in the second through tenth years, with cumulative incidences of 14% at 5 years and 21% at 10 years. Based on 10 studies with information available on fatal stroke, the pooled case fatality rate of subsequent stroke was 9.5% (95% CI, 5.9 – 13.8). Conclusions: One in five patients is expected to experience a subsequent stroke within 10 years after a TIA or minor stroke, with every tenth patient expected to die from their subsequent stroke.
C.4 Neurologic injury in pediatric patients cannulated for rescue extracorporeal life support
Authors: Buttle SG , Woodward K , Foster L , Yee P , Kirton A , Jamal S , Mineyko A , Blackwood J , Esser MJ
Published: May 2024

Background: Historical literature suggests the risk of neurologic injury in children supported by extracorporeal life support (ECLS) is between 10-20%, however recent studies suggest the incidence may be much higher. Methods: The Alberta Children’s Hospital (ACH) Rescue ECLS program cannulates patients who are then transferred to the partner program at Stollery Children’s Hospital. Data was systematically collected from all patients cannulated for Rescue ECLS at ACH October 2011 and May 2023. Neuroimaging (CT, MR) performed after cannulation was reviewed for evidence of ischemic and hemorrhagic strokes and hypoxic-ischemic brain injury. Results: Seventy-one patients were included in the Rescue ECLS cohort. Median age at cannulation was 1.74 years (range 0-17.6 years, 51% female). Survival to hospital discharge was 65%. Primary indication for ECLS included cardiac (42%), respiratory (33.3%), extracorporeal cardiopulmonary resuscitation (ECPR; 23.2%) and trauma (1.4%). Seventy four percent of the cohort underwent neuroimaging, of whom 67% had evidence of neurologic injury including stroke (ischemic 67%; hemorrhagic 50%) or hypoxic-ischemic injury (33%). Risk of neurologic injury did not differ by indication for ECLS. Conclusions: Neuroimaging abnormalities are present in most pediatric patients imaged post-cannulation for Rescue ECLS. Further research into modifiable risk factors for specific ECLS-related brain injuries may help to improve outcomes for survivors.
E.2 Proof of concept for liquid biopsy: positive correlation between extracellular vesicles shed by high grade gliomas and volume of hypervascular tumour tissue on MRI
Authors: Gaudette E , Willms M , Han J , Roy J , Weeks A , Schmidt M
Published: May 2024

Background: High grade gliomas (HGGs) shed extracellular vesicles (EVs) into the bloodstream. EV-derived RNA (EV-RNA) can be detected in plasma, making it a potential biomarker for HGG recurrence after treatment. We sought to establish a baseline relationship between EV-RNA in plasma and hypervascular HGG tissue on MRI. Methods: Eight patients with a new diagnosis of HGG had measurements of plasma EV-RNA and contemporaneous dynamic susceptibility contrast (DSC) MRI. Patient-specific median signal intensity of corpus callosum (mSI-CC) was determined from 10 measurements on the relative cerebral blood volume (rCBV) map. Tumour tissue with signal intensity > mSI-CC and > 2x, > 3x, > 4x and > 5x mSI-CC was segmented on the rCBV map. EV-RNA plasma concentration was correlated with tissue volumes. Results: Pearson correlation showed a significant positive relationship between EV-RNA plasma concentration and tissue volume with signal intensity > mSI-CC (r(6) = 0.899, p = 0.002). No significant relationship could be detected for progressively smaller tissue volumes with signal intensity > 2x, > 3x, > 4x and > 5x mSI-CC. Conclusions: EV-RNA plasma concentration correlates strongly with the total volume of hypervascular HGG tissue on DSC MRI at baseline and merits further evaluation as a biomarker of tumour behaviour in longitudinal imaging studies.
Spectral asymptotics for linear elasticity: the case of mixed boundary conditions
Authors: Capoferri Matteo , Mann Isabel
Published: May 2024

We establish two-term spectral asymptotics for the operator of linear elasticity with mixed boundary conditions on a smooth compact Riemannian manifold of arbitrary dimension. We illustrate our results by explicit examples in dimension two and three, thus verifying our general formulae both analytically and numerically.
Robotica: decoupled elastostatic stiffness modeling of hybrid robots
Authors: Wang Baoyu , Li Peixing , Yang Chao , Hu Xudong , Zhao Yanzheng
Published: May 2024

A decoupling method is proposed for the elastic stiffness modeling of hybrid robots based on the rigidity principle, screw theory, strain energy, and Castigliano’s second theorem. It enables the decoupling of parallel and serial modules, as well as the individual contributions of each elastic component to the mechanism’s stiffness performance. The method is implemented as follows: (1) formulate limb constraint wrenches and corresponding limb stiffness matrix based on the screw theory and strain energy, (2) formulate the overall stiffness matrix of parallel and serial modules corresponding to end of the hybrid robots based on the rigidity principle, principle of virtual work, the wrench transfer formula, and strain energy methods, and (3) obtain and decouple the overall stiffness matrix and deflection of the robot based on the Castigliano’s second theorem. Finally, A planar hybrid structure and the 4SRRR + 6R hybrid robot are used as illustrative examples to implement the proposed method. The results indicate that selectively enhancing the stiffness performance of the mechanism is the most effective approach.
Lesbians, Gays, and Bisexuals Asset-based Welfare and Housing in Great Britain
Authors: Matthews Peter , Barnett Camilla , Lambert Paul , Gregory Lee , Formby Eleanor
Published: May 2024

The role of housing in providing a welfare asset has been widely explored. With the growth in home ownership between 1979 and 2008 and erosion of the welfare state, housing wealth has become part of the welfare mix in the UK. Here, we present analysis of housing outcomes, as measured in the UK Household Longitudinal Survey (UKHLS), among people who identify as lesbian, gay, or bisexual in Great Britain. This shows that lesbian, gay, and bisexual (LGB) people have poorer housing outcomes than heterosexual counterparts: they are less likely to be homeowners; more likely to be private renters; and more likely to be social renters. With growing intergenerational inequalities in access to home ownership, we argue that, as openly LGB (and broader trans and queer) people being on average younger than the rest of the population, this could lead to LGB people, as a group, being excluded from asset-based welfare in the future as they age.
TWISTED GAN–GROSS–PRASAD CONJECTURE FOR CERTAIN TEMPERED L-PACKETS
Authors: Chen Rui , Gan Wee Teck
Published: May 2024

In this paper, we investigate the twisted GGP conjecture for certain tempered representations using the theta correspondence and establish some special cases, namely when the L-parameter of the unitary group is the sum of conjugate-dual characters of the appropriate sign.
The Democratization of Long-Distance Migration: Trajectories and Flows during the “Mobility Transition,” 1850–1910
Authors: Greefs Hilde , Winter Anne
Published: May 2024

This article analyzes and demonstrates the declining social selectivity of migration distance in Europe’s long nineteenth century and argues that this drove a radically new process of democratization of long-distance migration. It uses innovative spatial and quantitative analysis of nominal data on more than 5,000 international migrants who moved to the booming port city of Antwerp in present-day Belgium between 1850 and 1910. Examining the changes in migrants’ origins and trajectories on the one hand, and in their profiles in terms of gender and occupations on the other hand, it argues that the main evolutions observed represent an overall loosening of the ancien régime link between migration distance on the one hand and social selectivity on the other hand. By focusing on gender and social class as markers of social selectivity and by mapping the impressive expansion of the trajectories of Antwerp’s growing number of long-distance migrants, it lays bare the spatial, gender, and social dimensions that contributed to a general process of democratization of long-distance migration. As such, it sheds new light on the dynamics of Europe’s so-called “mobility transition” in the long nineteenth century.
Coupled Detachment Faulting and Hydrothermal Circulation at 49.7°E Southwest Indian Ridge Revealed by Seafloor Magnetism
Authors: Liu Long , Zhou Jianping , Wu Tao , Tao Chunhui , Wang Shishun , Su Zhaoyang , Li Qianyu , Chen Ming , Jie Tianyu , Sui Bin
Published: May 2024

Detachment faults at slow‐ and ultraslow‐spreading mid‐ocean ridges are essential for lithosphere‐hydrosphere interactions. However, their coupling with subseafloor hydrothermal circulation is poorly understood. Here, we investigated shallow hydrothermal fluid circulations in the active Dragon Horn detachment fault system of the Southwest Indian Ridge using combined near‐bottom magnetic anomaly data and rock magnetic analyses. We observed enhanced magnetic anomalies related to the high magnetization of basaltic country rocks and highly serpentinized (>80%) peridotite, whereas the hydrothermally altered basalts and sulfide deposits had weak magnetization and reduced magnetic anomalies. Therefore, the low‐magnetization zone was interpreted as a proxy for the hydrothermal fluid channel. The spatial distribution of the low‐magnetization zone revealed that the inactive Suye field expanded more than 500 m in diameter horizontally and ∼100 m vertically, and the active Longqi hydrothermal field had a >1 km fluid channel, both centered around the detachment fault fracture zone. Our results establish a robust link between detachment faulting and shallow hydrothermal circulation in which the detachment fault system provides critical fluid paths. Therefore, detachment tectonics are important elements for evolving seafloor hydrothermal fields along the Southwest Indian Ridge and possibly other slow‐ and ultraslow‐spreading mid‐ocean ridges globally.
A Novel Strategy for Automatic Selection of Cross‐Basin Data to Improve Local Machine Learning‐Based Runoff Models
Authors: Nai Congyi , Liu Xingcai , Tang Qiuhong , Liu Liu , Sun Siao , Gaffney Paul P. J.
Published: May 2024

Previous studies have shown that regional deep learning (DL) models can improve runoff prediction by leveraging large hydrological datasets. However, training a DL regional model using all data without screening may degrade local performance. This study focuses on constructing enhanced local models through the utilization of cross‐basin data. To this end, we propose an approach that employs a novel training strategy to optimize DL model training for specific basins. The approach measures the impact of any one basin's gradient on the loss of the basin of interest, providing insights into the relationships between different basins. The approach was validated using 531 basins from the CAMELS dataset. Results suggest that local performance degradation is a common occurrence in regional models, and imbalanced data are likely to result in a specific pattern dominating the entire regional model. In comparison to a regional model simply trained with all basins, the median Nash‐Sutcliffe efficiency (NSE) for our models is 0.031 higher. In particular, the increase in NSE can exceed 0.2 for some dry basins. Our findings indicate that this novel DL strategy can significantly improve model performance in specific basins using large hydrological datasets, while mitigating local performance loss.
The Art of Doing Fieldwork on the Moon
Authors: Betancourt Mark
Published: May 2024

How �early-career planetary scientists are preparing to support the astronauts who will return to the lunar surface and beyond.
2024 Could Be Among Most Active Hurricane Seasons Ever
Authors: van Deelen Grace
Published: May 2024

A new NOAA report predicts an extraordinarily active Atlantic hurricane season spurred by record ocean temperatures and a shift to La Ni�a conditions.