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Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease.

The purpose of this study was to compare ankle stability and dynamic single-leg balance between jumping athletes and non-athletes, and to examine the correlation between ankle stability and dynamic single-leg balance. Thirty-eight jumping athletes and thirty-seven non-athletes participated in this study. The Cumberland Ankle Instability Tool (CAIT) was used to assess ankle stability. The Y-Balance Test (YBT) was used to examine single-leg balance in the anterior (AN), posteromedial (PM), and posterolateral (PL) directions. The results show that 42.11% of jumping athletes and 21.62% of non-athletes exhibited chronic ankle instability (CAI) in their examined leg. In addition, jumping athletes exhibited significantly worse ankle stability than non-athletes (p = 0.038). The two groups showed no significant difference in the YBT scores in all directions (p = 0.113 AN, 0.567 PM, 0.542 PL). Very low correlations were found between the CAIT and the YBT scores in all directions (r < 0.107). In conclusion, single-leg jumping athletes experienced a higher prevalence of CAI and significantly worse ankle stability than non-athletes. However, the results of the YBT did not correlate strongly with the CAIT scores, suggesting an inability to predict dynamic single-leg balance deficits based on perceived ankle stability alone in this population.

Education policy is currently calling for wholistic reform towards the integration of Science, Technology, Engineering, and Mathematics (STEM). However, much of the calls lack practical advice or application to aid classroom and teaching professionals in this venture. Of particular interest should be how properties, such as barriers, of the individual disciplines may change in an integrated form. One such barrier that should be considered is that of anxiety. This review develops a novel framework for STEM anxiety in the educational context. This is accomplished through a review of anxiety literature within the individual disciplines, with reference to related psychological constructs. Literature was reviewed for definitions of anxiety within the disciplines, ways that disciplinary anxiety has been measured, and what antecedents were identified. Antecedents were taken from those that were explicitly identified, as well as those that were inferentially indicated in the definitions or the measurement instruments. The antecedents, or contributors, to the individual disciplinary anxieties were cross-referenced to generate a single list of potential antecedents that may impact learning within the integrated STEM space.

Fire is one of the most undesirable events onboard a ship. The engine room is one of the most critical spaces in the ship in terms of fire protection, as it includes machinery, hydrocarbon fuel systems, and different electrical equipment. With the phasing out of Halon 1301 as a fire suppressant over recent decades, there has been an intensive effort to explore the efficacy of water-mist spray in mitigating fires within machinery spaces. This exploration entails a comprehensive investigation through experimental and simulation studies aimed at identifying suppression mechanisms and evaluating their effectiveness. While experimental setups typically encompass measurements of gas temperature, thermal radiation heat flux, oxygen concentration, and fire extinction time, limited attention has been paid to quantifying the heat release rate (HRR), a crucial indicator of fire magnitude. Furthermore, research into shielded fire scenarios remains sparse, despite their significance in maritime fire dynamics. Addressing shielded fires with water mist proves particularly challenging due to the potential obstruction impeding the direct interaction between the fire source and the water droplets. In the existing literature, most of the computational fluid dynamics (CFD) modelling of fires and suppression was performed using a Fire Dynamics Simulator (FDS). Alternate studies were performed using FireFOAM. and very few employed FLUENT and other analogous software codes. In the majority of reported computational studies, the determination of HRR was typically relied upon for its calculation derived from the measured data of fuel mass loss rate. Moreover, certain studies were undertaken for numerical simulations without conducting thorough model validation, either by omitting validation altogether or solely validating against dry fire experiments (i.e., without water-mist suppression). This critical review of the literature has identified several notable research gaps in the context of extinguishing hydrocarbon fires utilising water-mist spray, warranting further investigations. Additionally, this review paper highlights recent advancements in both experimental and numerical investigations pertaining to the efficacy of water-mist fire-suppression systems in enclosed spaces regarding hydrocarbon fires.

A numerical investigation has been conducted to analyse the effect of wind on the vertical spread of fire through a front opening in a building’s external walls. The study utilises a building geometry established from previous experimental work conducted by the National Research Council of Canada (NRCC). A horizontal projection or a vertical spandrel is introduced above the opening of the compartment of fire origin. The purpose of the projection or spandrel is to inhibit the vertical spread of the fire, following the relevant requirements in the Australian National Construction Code (NCC). A computational fluid dynamics (CFD) package for fire-driven fluid flow, namely the Fire Dynamics Simulator (FDS), is employed to simulate the fire behaviour. The FDS model is validated against the NRCC’s experimental results, and a good agreement is achieved. Winds from three horizontal directions (front wind is normal to the opening, side wind is parallel to the opening, and back wind is from behind the building) have been investigated, with speeds ranging up to 10 m/s for each wind direction. Front wind speeds below 1 m/s are found to slightly enhance the vertical spread of the fire, while speeds exceeding 1 m/s are inclined to promote horizontal spread. The impact of side wind on the vertical fire spread was also found to vary with wind speed. The increase in the speed of back wind influences flame buoyancy, resulting in an augmented vertical fire spread. Furthermore, the numerical results reveal that a vertical spandrel of 1100 mm height is less effective in preventing vertical fire spread through openings, compared to a 1100 mm deep horizontal projection. The study suggests that the fire safety design in reducing the hazard of vertical fire spread through openings in buildings’ external walls could be further improved if the effect of wind is considered.

This manuscript summarizes the outcomes of the 6th EuroSpeleo Protection Symposium. Special emphasis was laid on presenting and discussing monitoring activities under the umbrella of the Habitats Directive (EU Council Directive 92/43/EEC) for habitat type 8310 "Caves not open to the public" and the Emerald Network. The discussions revealed a high level of variation in the currently conducted underground monitoring activities: there is no uniform definition of what kind of underground environments the "cave" habitat should cover, how often a specific cave has to be monitored, and what parameters should be measured to evaluate the conservation status. The variation in spatial dimensions in national definitions of caves further affects the number of catalogued caves in a country and the number of caves to be monitored. Not always participants are aware of the complete national monitoring process and that data sets should be freely available or easily accessible. The discussions further showed an inherent dilemma between an anticipated uniform monitoring approach with a coherent assessment methodology and, on the contrary, the uniqueness of caves and subterranean biota to be assessed – combined with profound knowledge gaps and a lack of resources. Nevertheless, some good practices for future cave monitoring activities have been identified by the participants: (1) Cave monitoring should focus on bio- and geodiversity elements alike; (2) Local communities should be involved, and formal agreements envisaged; (3) Caves must be understood as windows into the subterranean realm; (4) Touristic caves should not be excluded ad-hoc from regular monitoring; (5) New digital tools and open FAIR data infrastructures should be implemented; (6) Cave biomonitoring should focus on a large(r) biological diversity; and (7) DNA-based tools should be integrated. Finally, the importance of the 'forgotten' Recommendation No. 36 from the Bern Convention as a guiding legal European document was highlighted.

Astrocyte-specific ion pump α2-Na+/K+-ATPase plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Here, we test the effect of Atp1a2 mRNA-specific antisense oligonucleotides (ASOs) to induce α2-Na+/K+-ATPase knockdown in the widely used ALS animal model, SOD1*G93A mice. Two ASOs led to efficient Atp1a2 knockdown and significantly reduced SOD1 aggregation in vivo. Although Atp1a2 ASO-treated mice displayed no off-target or systemic toxicity, the ASO-treated mice exhibited an accelerated disease onset and shorter lifespan than control mice. Transcriptomics studies reveal downregulation of genes involved in oxidative response, metabolic pathways, trans-synaptic signaling, and upregulation of genes involved in glutamate receptor signaling and complement activation, suggesting a potential role for these molecular pathways in de-coupling SOD1 aggregation from survival in Atp1a2 ASO-treated mice. Together, these results reveal a role for α2-Na+/K+-ATPase in SOD1 aggregation and highlight the critical effect of temporal modulation of genetically validated therapeutic targets in neurodegenerative diseases.

Continental margins are transitional areas between the land and the deep ocean where large amounts of particulate matter are supplied, transported, and ultimately deposited in the deep sea. High-energy hydrodynamic processes such as storms, ocean currents, or internal waves and tides, as well as bottom trawling activities contribute to the resuspension and remobilization of these particles. These mechanisms favor their transference from the continental shelf to the continental slope and maintain high concentrations of particulate matter in the water column forming nepheloid layers. The temporal evolution of the hydrographic and nepheloid structure in the upper slope off Vancouver Island (British Columbia, Canada, NE Pacific) was assessed by analyzing 4 months (from mid-August to late-November 2018) of sensor data from Ocean Networks Canada (ONC) NEPTUNE cabled seafloor observatory. The distribution of particulate matter during the study period illustrated a well-defined turbidity structure consisting of surface nepheloid layers (SNLs) at 400 m depth. Moderate storm events occurred during fall when the more intense INLs were recorded at shelf-break depths. However, not all the INLs recorded during this period occurred in coincidence with these storms, indicating that these INL detachments were modulated by a different sediment resuspension mechanism. Analyses of fishing vessel activity during the study period revealed that trawlers operated over the same depth range as these INLs. Our results suggest that, in combination with the regional currents, the presence of continuous fishing along the continental slope off Vancouver Island contributes to the advection of suspended sediment particles, playing a major role in their transfer as nepheloid layers.

Background: Recurrent hiatal hernia remains a challenge. Methods: For initial repairs at our center: patients with 1 repair were compared to those who required reoperation for symptomatic recurrence. Subsequently, patients who had 1 repair at our center were compared to all patients who required reoperation (including initial repair at another center). Results: There were 401 repairs: 308 primary repairs at our center and 93 reoperations, 287/308 (93%) required 1 repair and 21/308 (7%) required reoperation. Comparing 1 repair versus 21 reoperations, risk factors were abdominoplasty odds ratio = 32.0 (4.1–250.6), P

Case. A 13-year-old skeletally immature female presenting with an anterior cruciate ligament (ACL) rupture after a noncontact injury was treated with an intraepiphyseal ACL reconstruction. Flexible instrumentation was utilized to drill a femoral tunnel with an anatomic starting point, with a trajectory that curved inferolaterally away from the physis. At three years postoperatively, she had returned to her preinjury functioning and did not display any lower limb length growth abnormalities. Conclusions. The novel application of curved guides and flexible instruments, with intraoperative fluoroscopy, facilitated growth plate avoidance and a successful outcome of ACL reconstruction in a skeletally immature patient.

Conventional (diesel-electric) submarines can provide improved stealth compared to nuclear submarines once submerged. This is because nuclear submarines are generally larger and are required to operate their nuclear reactors at all times, unlike diesel-electric submarines which are generally smaller and can run exclusively on batteries when submerged which generally requires fewer moving parts. These characteristics normally result in a smaller acoustic, thermal and magnetic signature which afford diesel-electric submarines greater stealth when submerged. However, the current underwater range and endurance is limited by the energy storage or generation for submerged operation. The application of emerging energy storage technology seeks to address this limitation and provide significant tactical and operational advantages to the conventional submarine operator. From a fire safety perspective, the potential addition of technologies such as rechargeable lithium-ion batteries, Air Independent Propulsion (AIP) systems and increasingly sophisticated electronic equipment dramatically changes the risk space in an already challenging and unforgiving underwater environment. This study reviews the functions, failure modes and maturity of emerging technologies that have serious submarine fire safety implications. A semi-quantitative assessment of the fire risk associated with potential large future conventional submarine design options for batteries and AIP is provided. This assessment concludes that lithium-ion batteries pose the greatest challenge with regard to integration into conventional submarines without compromising reliability or safety.

Lithium-ion batteries (LiBs) are a proven technology for energy storage systems, mobile electronics, power tools, aerospace, automotive and maritime applications. LiBs have attracted interest from academia and industry due to their high power and energy densities compared to other battery technologies. Despite the extensive usage of LiBs, there is a substantial fire risk associated with their use which is a concern, especially when utilised in electric vehicles, aeroplanes, and submarines. This review presents LiB hazards, techniques for mitigating risks, the suppression of LiB fires and identification of shortcomings for future improvement. Water is identified as an efficient cooling and suppressing agent and water mist is considered the most promising technique to extinguish LiB fires. In the initial stages, the present review covers some relevant information regarding the material constitution and configuration of the cell assemblies, and phenomenological evolution of the thermal runaway reactions, which in turn can potentially lead to flaming combustion of cells and battery assemblies. This is followed by short descriptions of various active fire control agents to suppress fires involving LiBs in general, and water as a superior extinguishing medium in particular. In the latter parts of the review, the phenomena associated with water mist suppression of LiB fires are comprehensively reviewed.

Discharge against medical advice (DAMA) can have detrimental effects on patient outcomes. Recently, the diagnosis of posttraumatic stress disorder (PTSD) has been linked with DAMA in the mental health setting. However, PTSD as a risk factor for DAMA in surgical patients has not received much consideration, although such patients may be at risk for triggering or amplification of PTSD symptoms perioperatively. We present the first case report series of three surgical patients with PTSD who left the hospital AMA. These cases differ markedly from DAMA in non-PTSD patients. In all three subjects, the stress of feeling misunderstood by clinicians and the distress of public detainment by hospital security in the setting of chronic PTSD led to aggressive and risky behavior. All three subjects represented a risk to themselves and to others at the time of DAMA. Finally, all three subjects were difficult to contact for follow-up or medical care and missed appointments.

Increasing development across the western United States (USA) elevates concerns about effects on wildlife resources; the golden eagle (Aquila chrysaetos) is of special concern in this regard. Knowledge of golden eagle abundance and distribution across the western USA must be improved to help identify and conserve areas of major importance to the species. We used distance sampling and visual mark-recapture procedures to estimate golden eagle abundance from aerial line-transect surveys conducted across four Bird Conservation Regions in the western USA between 15 August and 15 September in 2006-2010, 2012, and 2013. To assess golden eagle-habitat relationships at this scale, we modeled counts of golden eagles seen during surveys in 2006-2010, adjusted for probability of detection, and used land cover and other environmental factors as predictor variables within 20-km2 sampling units randomly selected from survey transects. We found evidence of positive relationships between intensity of use by golden eagles and elevation, solar radiation, and mean wind speed, and of negative relationships with the proportion of landscape classified as forest or as developed. The model accurately predicted habitat use observed during surveys conducted in 2012 and 2013. We used the model to construct a map predicting intensity of use by golden eagles during late summer across our ~2 million-km2 study area. The map can be used to help prioritize landscapes for conservation efforts, identify areas where mitigation efforts may be most effective, and identify regions for additional research and monitoring. In addition, our map can be used to develop region-specific (e.g., state-level) density estimates based on the latest information on golden eagle abundance from a late-summer survey and aid designation of geographic management units for the species.

The increasing emergence of new forms of multidrug resistance among human pathogenic bacteria, coupled with the consequent increase of infectious diseases, urgently requires the discovery and development of novel antimicrobial drugs with new modes of action. Most of the antibiotics currently available on the market were obtained from terrestrial organisms or derived semisynthetically from fermentation products. The isolation of microorganisms from previously unexplored habitats may lead to the discovery of lead structures with antibiotic activity. The deep-sea environment is a unique habitat, and deep-sea microorganisms, because of their adaptation to this extreme environment, have the potential to produce novel secondary metabolites with potent biological activities. This review covers novel antibiotics isolated from deep-sea microorganisms. The chemical classes of the compounds, their bioactivities, and the sources of organisms are outlined. Furthermore, the authors report recent advances in techniques and strategies for the exploitation of deep-sea microorganisms.

Abstract Background Although viscosupplementation is an effective symptomatic treatment for knee osteoarthritis (OA), the effect of longer term administration on articular cartilage has not been fully explored. We examined the effect of viscosupplementation with Hylan G-F 20 on knee cartilage over 2 years in patients with knee OA. Methods In this prospective, single-blind, parallel control group pilot study, 78 patients with symptomatic knee OA (Kellgren-Lawrence grade II and III) were assigned to either intervention group (n = 39 receiving 4 courses of 3 × 2.0 ml of intra-articular Hylan G-F 20 injections at 6 month intervals) or control group (n = 39 receiving usual care for knee OA without injections). Magnetic resonance imaging of the study knee was performed at baseline, 12 and 24 months. Cartilage volume and defects were assessed using validated methods. Results Fifty-five subjects (71%) completed 24 month follow up. Over 24 months, the intervention group had a reduced annual percentage rate of medial and lateral tibial cartilage volume loss (mean ± SD, -0.3 ± 2.7% and -1.4 ± 4.3%) compared with the control group (2.3 ± 2.6% and 1.4 ± 2.6%, P = 0.001 and 0.005 for difference, respectively). The intervention group also showed reduced cartilage defect score increment in the medial tibiofemoral compartment (0.1 ± 1.3) compared with the control group (0.8 ± 1.5, P = 0.05). Conclusions Six monthly intra-articular injections of Hylan G-F 20 administered to patients with symptomatic knee OA have a beneficial effect on knee cartilage preservation measured by both cartilage volume and cartilage defects. Hylan G-F 20 warrants further evaluation in larger clinical trials as a possible disease-modifying agent in the treatment of knee OA. Trial Registration The study was registered with ClinicalTrials.gov (NCT00393393).

Background: Youth sports coaches play a critical role in proper concussion recognition and management, reinforcing the need for coach concussion education. As of 2021, most states have statutory and policy measures mandating concussion education for coaches. In practice, these mandates have been enacted through state legislatures and their respective youth sport governing bodies. Prior studies have found significant variations in the contents of state-level concussion risk reduction policies and have raised questions about their specificity., Objective: To expand on previous analyses to provide an overview of youth sports coach concussion education, highlighting variations in state policies and discrepancies between state mandates and youth sport governing bodies., Methods: This report utilized qualitative content analysis to characterize and compare U.S. state and governing body concussion education requirements for youth sport coaches. State concussion statutes were identified via the National Conference of State Legislatures and Open States databases, and governing body handbooks/bylaws were obtained via their websites. Two researchers independently coded the policies, and discrepancies were resolved through consensus meetings with additional youth traumatic brain injury experts., Results: We found significant variability in educational requirements and their implementation. A majority (68%; n = 34) of states require the completion of concussion education training for coaches. Notably, many states designate responsibility for enforcement and implementation of provisions to another party but just four state statutes delineate explicit consequences for noncompliance. Additionally, only 12 state statutes extend mandates to noninterscholastic sports, limiting their reach. In most cases, independent sanctioning authorities implement more stringent policies than the minimum acceptable standard established by state law., Conclusion: Our findings provide a coded data set of youth coach concussion laws and independent sanctioning authority guidelines that can be used in future research efforts. Further research investigating a relationship between the strength of coach concussion education policies and relevant youth and adolescent concussion-related metrics is required., (© 2024 American Academy of Physical Medicine and Rehabilitation.)

BRAF V600E pediatric low-grade gliomas frequently transform into high-grade gliomas (HGG) and poorly respond to chemotherapy, resulting in high mortality. Although combined BRAF and MEK inhibition (BRAFi+MEKi) outperforms chemotherapy, ∼70% of BRAF V600E HGG patients are therapy resistant and undergo unbridled tumor progression. BRAF V600E glioma have an immune-rich microenvironment suggesting that they could be responsive to immunotherapy but effects of BRAFi+MEKi on anti-tumor immunity are unclear. Using patient tumor tissue before and after BRAFi+MEKi, two novel syngeneic murine models of BRAF V600E HGG, and patient-derived cell lines, we examined the effects of clinically relevant BRAFi+MEKi with dabrafenib and trametinib on tumor growth, cell states, and tumor-infiltrating T cells. We find that BRAFi+MEKi treatment: i) upregulated programmed cell death protein-1 (PD-1) signaling genes and PD-1 ligand (PD-L1) protein expression in murine BRAF V600E HGG by stimulating IFNγ and IL-27, ii) attenuated T cell activity by IL-23, IL-27 and IL-32 production, which can promote the expansion of regulatory T cells, and iii) induced glial differentiation linked to a therapy-resistant PD-L1+ compartment through Galectin-3 secretion by tumor cells. Murine BRAF V600E HGG shrinkage by BRAFi+MEKi is associated with the upregulation of interferon-gamma response genes, MHC class I/II expression, and antigen presentation and processing programs, indicative of increased anti-tumor immunity. Combined BRAFi+MEKi with therapeutic antibodies inhibiting the PD-1 and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) immune checkpoints re-activate T cells and provide a survival benefit over single therapy in a T cell-dependent manner. The quadruple treatment overcame BRAFi+MEKi resistance by invigorating T cell-mediated anti-tumor immunity in murine BRAF V600E HGG. PD-L1 expression was elevated in human BRAF-mutant versus BRAF-wildtype glioblastoma clinical specimen, complementing experimental findings and suggesting translational relevance for patient care.

Protective headgear effects measured in the laboratory may not always translate to the field. In this study, we evaluated the impact attenuation capabilities of a commercially available padded helmet shell cover in the laboratory and on the field. In the laboratory, we evaluated the padded helmet shell cover's efficacy in attenuating impact magnitude across six impact locations and three impact velocities when equipped to three different helmet models. In a preliminary on-field investigation, we used instrumented mouthguards to monitor head impact magnitude in collegiate linebackers during practice sessions while not wearing the padded helmet shell covers (i.e., bare helmets) for one season and whilst wearing the padded helmet shell covers for another season. The addition of the padded helmet shell cover was effective in attenuating the magnitude of angular head accelerations and two brain injury risk metrics (DAMAGE, HARM) across most laboratory impact conditions, but did not significantly attenuate linear head accelerations for all helmets. Overall, HARM values were reduced in laboratory impact tests by an average of 25% at 3.5 m/s (range: 9.7 to 39.6%), 18% at 5.5 m/s (range: - 5.5 to 40.5%), and 10% at 7.4 m/s (range: - 6.0 to 31.0%). However, on the field, no significant differences in any measure of head impact magnitude were observed between the bare helmet impacts and padded helmet impacts. Further laboratory tests were conducted to evaluate the ability of the padded helmet shell cover to maintain its performance after exposure to repeated, successive impacts and across a range of temperatures. This research provides a detailed assessment of padded helmet shell covers and supports the continuation of in vivo helmet research to validate laboratory testing results., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Objective: Chiari malformation type I (CM-I) is defined by the herniation of the cerebellar tonsils into the spinal canal. When symptomatic, surgical decompression is recommended. Reported CM-I reoperation rates have ranged from 3% to 30%. However, the relationship between patient age at first surgical intervention and the likelihood of reoperation and postoperative complications remains poorly characterized. Therefore, this study aimed to determine whether patient age was associated with reoperation and complication rates., Methods: Patients 0-21 years old with a diagnosis of CM-I and surgical decompression were queried from the 2007-2021 MarketScan databases. Patient sex, age at time of first procedure, comorbidities, 90-day postoperative complications, and reoperations were identified. Bootstrap-augmented binary classifiers were constructed to determine the optimal timing of first surgical decompression with respect to all-cause 90-day postoperative complications and reoperation. Multivariate logistic regression models were built to assess the relationship between age, sex, and comorbidities and the likelihood of reoperation and complications following surgical decompression., Results: A total of 2675 patients were included for analysis of 90-day postoperative complications, and 1157 were included in the reoperation analysis cohort. A total of 524 patients (19.6%) experienced a complication within 90 days of surgical decompression, and 84 patients (7.3%) had reoperations. On multivariate regression, increased age was an independent predictor of a reduced likelihood of both reoperations (OR 0.94, 95% CI 0.90-0.98; p < 0.01) and 90-day postoperative complications (OR 0.96, 95% CI 0.94-0.98; p < 0.01). The optimal age cutoff to predict both complications and reoperations was 4 years. For patients ages 4 years and older, both the reoperation rate (5.5% vs 13.2%, p < 0.01) and 90-day postoperative complication rates (18.4% vs 27.7%; p < 0.01) were significantly less than those for children 3 years and younger., Conclusions: In a national cohort of pediatric patients undergoing surgically managed CM-I, there was a significantly increased likelihood of reoperation and complications in patients ages 3 years and younger. Although CM-I decompression should not be postponed in the face of progressive neurological deficits, the authors' findings suggest that delaying surgery until after the age of 3 years, when medically feasible, may help mitigate adverse events.

While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric posterior fossa brain tumors, and evaluate its performance on a diverse, realistic, multi-center cohort. Pediatric brain tumors were targeted due to the scarcity of such datasets, even in tertiary care hospitals. Our platform orchestrates federated training for joint tumor classification and segmentation across 19 international sites. FL-PedBrain exhibits less than a 1.5% decrease in classification and a 3% reduction in segmentation performance compared to centralized data training. FL boosts segmentation performance by 20 to 30% on three external, out-of-network sites. Finally, we explore the sources of data heterogeneity and examine FL robustness in real-world scenarios with data imbalances., (© 2024. The Author(s).)

Objective: Wearable devices are developed to measure head impact kinematics but are intrinsically noisy because of the imperfect interface with human bodies. This study aimed to improve the head impact kinematics measurements obtained from instrumented mouthguards using deep learning to enhance traumatic brain injury (TBI) risk monitoring., Methods: We developed one-dimensional convolutional neural network (1D-CNN) models to denoise mouthguard kinematics measurements for tri-axial linear acceleration and tri-axial angular velocity from 163 laboratory dummy head impacts. The performance of the denoising models was evaluated on three levels: kinematics, brain injury criteria, and tissue-level strain and strain rate. Additionally, we performed a blind test on an on-field dataset of 118 college football impacts and a test on 413 post-mortem human subject (PMHS) impacts., Results: On the dummy head impacts, the denoised kinematics showed better correlation with reference kinematics, with relative reductions of 36% for pointwise root mean squared error and 56% for peak absolute error. Absolute errors in six brain injury criteria were reduced by a mean of 82%. For maximum principal strain and maximum principal strain rate, the mean error reduction was 35% and 69%, respectively. On the PMHS impacts, similar denoising effects were observed and the peak kinematics after denoising were more accurate (relative error reduction for 10% noisiest impacts was 75.6%)., Conclusion: The 1D-CNN denoising models effectively reduced errors in mouthguard-derived kinematics measurements on dummy and PMHS impacts., Significance: This study provides a novel approach for denoising head kinematics measurements in dummy and PMHS impacts, which can be further validated on more real-human kinematics data before real-world applications.

Objective: The goal of this study was to survey the members of the American Society of Pediatric Neurosurgeons (ASPN) to assess the prevalence and associated risks of burnout among pediatric neurosurgeons. The authors aimed to identify the factors that most significantly contributed to this risk to provide a baseline group of characteristics to improve physician well-being., Methods: Institutional Review Board approval from the University of Arizona was obtained, and the 7-question and 9-question Mayo Physician Well-Being Index (WBI) was distributed to members of the ASPN (n = 275). This index screens for many different aspects of distress for physicians, including burnout risk, stress, depression, fatigue, suicidal ideation, and low career satisfaction., Results: An analysis of 111 pediatric neurosurgeons (111/275 [40% response rate]) was completed. Respondent ages were distributed, with those aged 56-60 years representing the highest proportion (20%). University practice represented a majority (72%). One-third (32%) of respondents reported practicing greater than 25 years, and most physicians in the survey were married (76%). One-third of surgeons spend 61-70 hours working per week (33%), and a plurality are on call between 6 and 10 days per month (42%). Most surgeons reported treating fewer than 200 cases per year (37% reported 100-150 cases; 23%, 151-200). Most pediatric neurosurgeons (63%) stated their annual salary was sufficient. Analysis of each WBI question was performed to identify which factors specifically contributed to the risk of burnout. An overwhelming majority of respondents reported that they make significant efforts to do at least one thing each week that brings them joy (97%), and they either agree or strongly agree that they perform meaningful work (98% of all participants, 97% of females, and 98% of men, p = 0.010). Nearly half of all respondents (49%) reported feelings of burnout and a majority of them were female (67% of women and 42% of men, p = 0.021). Time, environment, case volumes, and quality-of-life concerns are all factors that significantly contribute to the overall risk of burnout and well-being., Conclusions: This survey study of the ASPN membership revealed a 49% rate of burnout with females at higher risk (67%). Factors associated with burnout were salary, more than 10 days on call per month, electronic medical record stressors, and work-life incongruity. The aforementioned notwithstanding, respondents believe pediatric neurosurgery is a meaningful career. This study provides evidence supporting a moral imperative toward recognition of burnout symptoms and a pivot point toward implementing change.

Objective: Hydrocephalus is a challenging neurosurgical condition due to nonspecific symptoms and complex brain-fluid pressure dynamics. Typically, the assessment of hydrocephalus in children requires radiographic or invasive pressure monitoring. There is usually a qualitative focus on the ventricular spaces even though stress and shear forces extend across the brain. Here, the authors present an MRI-based vector approach for voxelwise brain and ventricular deformation visualization and analysis., Methods: Twenty pediatric patients (mean age 7.7 years, range 6 months-18 years; 14 males) with acute, newly diagnosed hydrocephalus requiring surgical intervention for symptomatic relief were randomly identified after retrospective chart review. Selection criteria included acquisition of both pre- and posttherapy paired 3D T1-weighted volumetric MRI (3D T1-MRI) performed on 3T MRI systems. Both pre- and posttherapy 3D T1-MRI pairs were aligned using image registration, and subsequently, voxelwise nonlinear transformations were performed to derive two exemplary visualizations of compliance: 1) a whole-brain vector map projecting the resulting deformation field on baseline axial imaging; and 2) a 3D heat map projecting the volumetric changes along ventricular boundaries and the brain periphery., Results: The patients underwent the following interventions for treatment of hydrocephalus: endoscopic third ventriculostomy (n = 6); external ventricular drain placement and/or tumor resection (n = 10); or ventriculoperitoneal shunt placement (n = 4). The mean time between pre- and postoperative imaging was 36.5 days. Following intervention, the ventricular volumes decreased significantly (mean pre- and posttherapy volumes of 151.9 cm3 and 82.0 cm3, respectively; p < 0.001, paired t-test). The largest degree of deformation vector changes occurred along the lateral ventricular spaces, relative to the genu and splenium. There was a significant correlation between change in deformation vector magnitudes within the cortical layer and age (p = 0.011, Pearson), as well as between the ventricle size and age (p = 0.014, Pearson), suggesting higher compliance among infants and younger children., Conclusions: This study highlights an approach for deformation analysis and vector mapping that may serve as a topographic visualizer for therapeutic interventions in patients with hydrocephalus. A future study that correlates the degree of cerebroventricular deformation or compliance with intracranial pressures could clarify the potential role of this technique in noninvasive pressure monitoring or in cases of noncompliant ventricles.

Objective: The machine-learning head model (MLHM) to accelerate the calculation of brain strain and strain rate, which are the predictors for traumatic brain injury (TBI), but the model accuracy was found to decrease sharply when the training/test datasets were from different head impacts types (i.e., car crash, college football), which limits the applicability of MLHMs to different types of head impacts and sports. Particularly, small sizes of target dataset for specific impact types with tens of impacts may not be enough to train an accurate impact-type-specific MLHM., Methods: To overcome this, we propose data fusion and transfer learning to develop a series of MLHMs to predict the maximum principal strain (MPS) and maximum principal strain rate (MPSR)., Results: The strategies were tested on American football (338), mixed martial arts (457), reconstructed car crash (48) and reconstructed American football (36) and we found that the MLHMs developed with transfer learning are significantly more accurate in estimating MPS and MPSR than other models, with a mean absolute error (MAE) smaller than 0.03 in predicting MPS and smaller than [Formula: see text] in predicting MPSR on all target impact datasets. High performance in concussion detection was observed based on the MPS and MPSR estimated by the transfer-learning-based models., Conclusion: The MLHMs can be applied to various head impact types for rapidly and accurately calculating brain strain and strain rate., Significance: This study enables developing MLHMs for the head impact type with limited availability of data, and will accelerate the applications of MLHMs.

Objective: In 2019, 22% of adults in the United States reported speaking a language other than English at home, representing 52% growth since 2000. This diversity in languages - and resulting possible communication barriers - represents a potential challenge to effective care. In this manuscript, we summarize clinical outcomes and healthcare utilization patterns of adult and pediatric neurosurgical patients who are non-English primary language speakers (NEPLS)., Methods: We systematically queried 5 databases from inception through October 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to identify studies for inclusion. The Newcastle-Ottawa Scale was used to assess the quality of studies. Additionally, a retrospective chart review was conducted to assess differences in postoperative communication patterns in a cohort of English and Spanish speaking patients with craniosynostosis at our institution., Results: Our search yielded 442 abstracts; ten were included in the final cohort. Outcomes for 973 unique NEPLS with a neurosurgical condition were included; Spanish was the most represented language. Delivery and timing of surgical treatment was the most frequently reported metric; 75% of studies demonstrated a statistically significant delay in time to surgery or decreased likelihood for NEPLS to receive surgical treatment. Length of stay was reported in 3 studies; all demonstrated that NEPLS had longer length of stay., Conclusions: There is a paucity of literature reporting outcomes among NEPLS. It is critical to examine NEPLS patients' outcomes and experiences, as language barriers are potentially modifiable demographic factors. We present a framework that demonstrates opportunities for further research to improve quality of care., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF)., Methods: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio., Results: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95)., Conclusions: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

Competing Interests: The Authors declare no conflicts of interest in relation to this study.

Introduction: Invasive intracranial electroencephalography (IEEG) is advantageous for identifying epileptogenic foci in pediatric patients with medically intractable epilepsy. Patients with behavioral challenges due to autism, intellectual disabilities, and hyperactivity have greater difficulty tolerating prolonged IEEG recording and risk injuring themselves or others. There is a need for therapies that increase the safety of IEEG but do not interfere with IEEG recording or prolong hospitalization. Dexmedetomidine Hydrochloride's (DH) use has been reported to improve safety in patients with behavioral challenges during routine surface EEG recording but has not been characterized during IEEG. Here we evaluated DH administration in pediatric patients undergoing IEEG to assess its safety and impact on the IEEG recordings., Methods: A retrospective review identified all pediatric patients undergoing IEEG between January 2016 and September 2022. Patient demographics, DH administration, DH dose, hospital duration, and IEEG seizure data were analyzed. The number of seizures recorded for each patient was divided by the days each patient was monitored with IEEG. The total number of seizures, as well as seizures per day, were compared between DH and non-DH patients via summary statistics, multivariable linear regression, and univariate analysis. Other data were compared across groups with univariate statistics., Results: Eighty-four pediatric patients met the inclusion criteria. Eighteen (21.4 %) received DH treatment during their IEEG recording. There were no statistical differences between the DH and non-DH groups' demographic data, length of hospital stays, or seizure burden. Non-DH patients had a median age of 12.0 years (interquartile range: 7.25-15.00), while DH-receiving patients had a median age of 8.0 years old (interquartile range: 3.00-13.50) (p = 0.07). The non-DH cohort was 57.6 % male, and the DH cohort was 50.0 % male (p = 0.76). The median length of IEEG recordings was 5.0 days (interquartile range: 4.00-6.25) for DH patients versus 6.0 days (interquartile range: 4.00-8.00) for non-DH patients (p = 0.25). Median total seizures recorded in the non-DH group was 8.0 (interquartile range: 5.00-13.25) versus 15.0 in the DH group (interquartile range: 5.00-22.25) (p = 0.33). Median total seizures per day of IEEG monitoring were comparable across groups: 1.50 (interquartile range: 0.65-3.17) for non-DH patients compared to 2.83 (interquartile range: 0.89-4.35) (p = 0.25) for those who received DH. Lastly, non-DH patients were hospitalized for a median of 8.0 days (interquartile range: 6.00-11.25), while DH patients had a median length of stay of 7.00 days (interquartile range: 5.00-8.25) (p = 0.27). No adverse events were reported because of DH administration., Conclusions: Administration of DH was not associated with adverse events. Additionally, the frequency of seizures captured on the IEEG, as well as the duration of hospitalization, were not significantly different between patients receiving and not receiving DH during IEEG. Incorporating DH into the management of patients with behavioral dyscontrol and intractable epilepsy may expand the use of IEEG to patients who previously could not tolerate it, improve safety, and preserve epileptic activity during the recording period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To determine if differences exist in postoperative communication patterns or healthcare use among English-speaking patients (ESPs) and Spanish-speaking patients (SSPs) with childhood hydrocephalus., Study Design: A single-institution, retrospective cohort study was conducted. Through simple random sampling, 50 ESPs and 50 SSPs (<18 years old) who underwent a ventriculoperitoneal shunt or endoscopic third ventriculostomy were identified. Demographics, communication with clinic (eg, number of calls or messages postoperatively), and healthcare use were collected. Multiple linear regressions assessed the significance of predictors on communication frequency and use., Results: SSPs were more likely to have a comorbidity and ventriculoperitoneal shunt than ESPs. SSPs had longer median postoperative length of stay (P < .01) and 30-day readmission rate (P < .01) than ESPs. Only 18% of SSPs communicated with clinic; 11 total calls or messages were from SSPs vs 57 from ESPs (P < .01). The most common reason for outreach among both cohorts was a new symptom. ESP outreach most frequently resulted in reassurance or medical course changes on an outpatient basis (30% ESPs vs 0% SSPs; P = .04), whereas SSP outreach most frequently resulted in guidance to present to the emergency department (3% ESPs vs 36% SSPs; P < .01). Language remained a significant predictor for number of calls or messages, even after adjusting for comorbidity, operation type, and insurance (P < .01)., Conclusions: Despite having more complex disease, only 18% of SSPs communicated with the neurosurgical team postoperatively and were more frequently sent to the emergency department for management. Future research will explore communication barriers and preferences to ensure postoperative care is timely and patient centered., Competing Interests: Declaration of Competing Interest This publication was generously supported by the Stanford Maternal and Child Health Research Institute Structural Racism, Social Injustice and Health Disparities Program (to L.M.P.) as well as the Stanford University Medical Scholars Program (to G.R.C.). The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to better understand the safety and efficacy of laser interstitial thermal therapy (LITT) for children with medically refractory epilepsy., Methods: Thirty-seven consecutive pediatric epilepsy patients at a single pediatric center who underwent LITT ablation of epileptogenic foci between May 2017 and December 2021 were retrospectively reviewed. Patient demographics, medication use, seizure frequency, prior surgical interventions, procedural details, and pre- and postoperative seizure history were analyzed., Results: Thirty-seven pediatric patients (24 male, 13 female) with severe medically refractory epilepsy were included; all underwent stereo-electroencephalography (SEEG) prior to LITT. The SEEG electrode placement was based on the preoperative workup and tailored to each patient by the epileptologist and neurosurgeons working together to identify the epileptic network and hopefully quiet borders. Seizure onset was at a mean age of 2.70 ± 2.82 years (range 0.25-12 years), and the mean age at the time of LITT was 9.46 ± 5.08 years (range 2.41-17.86 years). Epilepsy was lesional in 23 patients (18 tuberous sclerosis, 4 focal cortical dysplasia, 1 gliosis) and nonlesional in 14. Eighteen patients had prior surgical interventions including open resections (n = 13: 11 single and 2 multiple), LITT (n = 4), or both (n = 1). LITT targeted a region adjacent to the previous target in 5 cases. The median number of lasers placed during the procedure was 3 (range 1-5). Complications occurred in 14 (37.8%) cases, only 3 (8.11%) of which resulted in a permanent deficit: 1 venous hemorrhage requiring evacuation following laser ablation, 1 aseptic meningitis, 2 immediate postoperative seizures, and 10 neurological deficits (7 transient and 3 permanent). Postoperatively, 22 (59.5%) patients were seizure free at the last follow-up (median follow-up 18.35 months, range 7.40-48.76 months), and the median modified Engel class was I (Engel class I in 22 patients, Engel class II in 2, Engel class III in 2, and Engel class IV in 11). Patients having tried a greater number of antiseizure medications before LITT were less likely to achieve seizure improvement (p = 0.046) or freedom (p = 0.017). Seizure improvement following LITT was associated with a shorter duration of epilepsy prior to LITT (p = 0.044), although postoperative seizure freedom was not associated with a shorter epilepsy duration (p = 0.667). Caregivers reported postoperative neurocognitive improvement in 17 (45.9%) patients., Conclusions: In this large single-institution cohort of pediatric patients with medically refractory seizures due to various etiologies, LITT was a relatively safe and effective surgical approach for seizure reduction and seizure freedom at 1 year of follow-up.

Background: Traumatic brain injury can be caused by head impacts, but many brain injury risk estimation models are not equally accurate across the variety of impacts that patients may undergo, and the characteristics of different types of impacts are not well studied. We investigated the spectral characteristics of different head impact types with kinematics classification., Methods: Data were analyzed from 3262 head impacts from lab reconstruction, American football, mixed martial arts, and publicly available car crash data. A random forest classifier with spectral densities of linear acceleration and angular velocity was built to classify head impact types (e.g., football, car crash, mixed martial arts). To test the classifier robustness, another 271 lab-reconstructed impacts were obtained from 5 other instrumented mouthguards. Finally, with the classifier, type-specific, nearest-neighbor regression models were built for brain strain., Results: The classifier reached a median accuracy of 96% over 1000 random partitions of training and test sets. The most important features in the classification included both low- and high-frequency features, both linear acceleration features and angular velocity features. Different head impact types had different distributions of spectral densities in low- and high-frequency ranges (e.g., the spectral densities of mixed martial arts impacts were higher in the high-frequency range than in the low-frequency range). The type-specific regression showed a generally higher R 2 value than baseline models without classification., Conclusion: The machine-learning-based classifier enables a better understanding of the impact kinematics spectral density in different sports, and it can be applied to evaluate the quality of impact-simulation systems and on-field data augmentation., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2023. Production and hosting by Elsevier B.V.)