Background: Meningiomas are the most common intracranial tumor with surgery, dural margin treatment, and radiotherapy as cornerstones of therapy. Response to treatment continues to be highly heterogeneous even across tumors of the same grade. Methods: Using a cohort of 2490 meningiomas in addition to 100 cases from the prospective RTOG-0539 phase II clinical trial, we define molecular biomarkers of response across multiple different, recently defined molecular classifications and use propensity score matching to mimic a randomized controlled trial to evaluate the role of extent of resection, dural marginal resection, and adjuvant radiotherapy on clinical outcome. Results: Gross tumor resection led to improved progression-free-survival (PFS) across all molecular groups (MG) and improved overall survival in proliferative meningiomas (HR 0.52, 95%CI 0.30-0.93). Dural margin treatment (Simpson grade 1/2) improved PFS versus complete tumor removal alone (Simpson 3). MG reliably predicted response to radiotherapy, including in the RTOG-0539 cohort. A molecular model developed using clinical trial cases discriminated response to radiotherapy better than standard of care grading in multiple cohorts (ΔAUC 0.12, 95%CI 0.10-0.14). Conclusions: We elucidate biological and molecular classifications of meningioma that influence response to surgery and radiotherapy in addition to introducing a novel molecular-based prediction model of response to radiation to guide treatment decisions.

Background: Meningiomas are the most common intracranial tumor, graded from 1 (benign) to 3 (malignant). The aim of this study was to identify clinical features associated with overall survival (OS), progression-free survival (PFS) and functional status for malignant meningiomas. Methods: Demographic, clinical and histopathological data from grade 3 intracranial meningioma cases were identified in the clinical databases from seven sites in North America and Europe from 1991-2022. Summary statistics and Kaplan-Meier OS and PFS curves were generated. Results: We identified 108 patients, with a median age 65 years (IQR: 52, 72) and 53.7% were female. Median OS was 109 months (95% CIs: 88, 227), and 5-year OS rate was 65% (95% CIs: 56, 76). Median PFS was 38 months (95% CIs: 24, 56) and 5-year PFS rate was 37% (95% CIs: 28, 49). OS and PFS were significantly lower in patients aged ≥65 years. Median preoperative KPS score was 80 (IQR: 70, 90), postoperatively KPS was 90 (IQR: 70, 98) and 1-year follow-up KPS was 70 (IQR: 50, 80). Conclusions: This study provides robust survival, recurrence and functional data for grade 3 meningiomas in North America and Europe over a 30-year period.

Background: The coronavirus disease 2019 (COVID-19) pandemic has led the implementation of institutional infection control protocols. This study will determine the effects of these protocols on outcomes of acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT). Methods: Uninterrupted time series analysis of the impact of COVID-19 safety protocols on AIS patients undergoing EVT. We analyze data from prospectively collected quality improvement databases at 6 centers from March 11, 2019 to March 10, 2021. The primary outcome is 90-day modified Rankin Score (mRS). The secondary outcomes are angiographic time metrics. Results: Preliminary analysis of one stroke center included 214 EVT patients (n=150 pre-pandemic). Baseline characteristics were comparable between the two periods. Time metrics “last seen normal to puncture” (305.7 vs 407.2 min; p=0.05) and “hospital arrival to puncture” (80.4 vs 121.2 min; p=0.04) were significantly longer during pandemic compared to pre-pandemic. We found no significant difference in 90-day mRS (2.0 vs 2.2; p=0.506) or successful EVT rate (89.6% vs 90%; p=0.93). Conclusions: Our results indicate an increase in key time metrics of EVT in AIS during pandemic, likely related to infection control measures. Despite the delays, we found no difference in clinical outcomes between the two periods.

Background: The coronavirus disease 2019 (COVID-19) pandemic has led an implementation of institutional infection control protocols. This study will determine the effects of these protocols on outcomes of acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT). Methods: Uninterrupted time series analysis of the impact of COVID-19 safety protocols on AIS patients undergoing EVT. We analyze data from prospectively collected quality improvement databases at 9 centers from March 11, 2019 to March 10, 2021. The primary outcome is 90-day modified Rankin Score (mRS). The secondary outcomes are angiographic time metrics. Results: Preliminary analysis of one stroke center included 214 EVT patients (n=144 pre-pandemic). Baseline characteristics were comparable between the two periods. Time metrics “last seen normal to puncture” (305.7 vs 407.2 min; p=0.05) and “hospital arrival to puncture” (80.4 vs 121.2 min; p=0.04) were significantly longer during pandemic compared to pre-pandemic. We found no significant difference in 90-day mRS (2.0 vs 2.2; p=0.506) or successful EVT rate (89.6% vs 90%; p=0.93). Conclusions: Our results indicate an increase in key time metrics of EVT in AIS during the pandemic, likely related to infection control measures. Despite the delays, we found no difference in clinical outcomes between the two periods.

Introduction: Emergency department (ED) patients with cellulitis that are treated with intravenous (IV) antibiotics may be eligible for outpatient parenteral antibiotic therapy (OPAT). The primary objective of this study was to determine whether the implementation of an OPAT clinic results in decreased hospitalization and return ED visits for patients treated with IV antibiotics. Methods: We conducted a before-after implementation study involving adults (age >=18 years) that presented to two tertiary care EDs with cellulitis and were treated with IV antibiotics. The intervention was referral to an infectious disease physician within one week of the index ED visit at the newly created OPAT clinic. The primary outcomes were hospital admission and return ED visits within 14 days. Secondary outcomes were treatment failure (admission after 48 hours of OPAT) and adverse events (e.g. vomiting, diarrhea). We conducted an interrupted time series analysis from January to December both pre-intervention (2013) and post-intervention (2015), with 24 monthly data points. The year of clinic implementation (2014) was considered a transition period. A segmented non-linear regression autoregressive error model was used to aggregate the monthly data to evaluate the effectiveness of the intervention. Results: A total of 1,666 patients met inclusion criteria: 858 pre-intervention (mean age 59 years, 53.1% male) and 808 post-intervention (mean age 62 years, 54.5% male). Hospitalization rates were not significantly higher one year after clinic implementation (p = 0.53) although there was a non-statistically significant gradual increase of 0.8% per month (95%CI -0.3% to 1.9%). One year after introduction of the OPAT clinic, return ED visits were significantly lower (change in intercept -24.4%, 95%CI -34.2% to -14.6%; p < 0.001), followed by an additional drop of 1.4% per month (95%CI -2.1% to -0.6%; p = 0.002). By the end of the study, return visits were 40.7% lower (95%CI 25.6% to 55.9%) than if the intervention had not been introduced. Treatment failure rates were <2% and adverse events were <5% in both groups. Conclusion: Implementation of an OPAT clinic significantly reduced return ED visits for cellulitis, which is critically important given the current ED overcrowding crisis. There was no significant change in hospital admission rates. There were low rates of treatment failures and adverse events. An OPAT clinic should be considered to reduce ED crowding while maintaining safe patient care.

We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.

Introduction: A significant gap exists between the number of people waiting for an organ and donors. There are currently 1,628 people awaiting organ donation in Ontario alone. In 2018 to date, 310 donors have donated 858 organs. The purpose of this study was to determine whether there were missed donors in the Emergency Department (ED) and by what percent those missed donors would increase organ donation overall. Methods: This was a health records and organ donation database review of all patients who died in the ED at a large academic tertiary care center with 2 campuses and 160,000 visits per year. Patients were included from November 1, 2014 – October 31, 2017. We collected data on demographics, cause of death, and suitability for organ donation. Data was cross-referenced between hospital records and the provincial organ procurement organization called Trillium Gift of Life Network (TGLN) to determine whether patients were appropriately referred for consideration of donation in a timely manner. Potential missed donors were manually screened for suitability according to TGLN criteria. We calculated simple descriptive statistics for demographic data and the primary outcome. The primary outcome was percentage of potential organ donors missed in the Emergency Department (ED). Results: There were 606 deaths in the ED from November 1, 2014 – October 31, 2017. Patients were an average of 71 years old, 353 (58%) were male, and 75 (12%) died of a traumatic cause. TGLN was not contacted in 12 (2%) of cases. During this period there were two donors from the ED and 92 from the ICU. There were ten missed potential donors. They were an average of 67 years, 7 (70%) were male, and 2 (20%) died of a traumatic cause. In all ten cases, patients had withdrawal of life sustaining measures for medical futility prior to TGLN being contacted for consideration of donation. There could have been an addition seven liver, six pancreatic islet, four small bowel, and seven kidney donors. The ten missed ED donors could have increased total donors by 11%. Conclusion: The ED is a significant source of missed organ donors. In all cases of missed organ donation, patients had withdrawal of life sustaining measures prior to TGLN being called. In the future, it is essential that all patients have an organ procurement organization such as TGLN called prior to withdrawal of life sustaining measures to ensure that no opportunity for consideration of organ donation is missed.

Greenhouse studies were conducted to investigate the basis for effective field control of yellow nutsedge (Cyperus esculentus L. var. esculentus) when atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-s-trizine] was applied late postemergence. Yellow nutsedge responded similarly to atrazine applied preemergence, early postemergence, or late postemergence. Yellow nutsedge growing with or without the presence of the mother tuber responded similarly to atrazine applied early postemergence. Atrazine application to the soil resulted in much greater yellow nutsedge injury than foliar application. The addition of oil enhanced atrazine activity when foliarly applied, but not when soil applied. Simulated rainfall immediately after postemergence applications enhanced yellow nutsedge control more than when simulated rainfall was delayed. The primary roots of yellow nutsedge appeared to be more important than other underground absorbing areas for atrazine uptake in young plants. Plants from tubers originating from lower soil depths produced secondary roots deeper, and these plants were less affected by atrazine applied preemergence than plants originating from tubers closer to the soil surface. A considerable reduction in atrazine activity was obtained when tubers were planted into soil 1 month after atrazine application.

Introduction: Cycling as a form of active transportation is popular in many urban communities. However, little is known about the prevalence and circumstances of cycling injuries, particularly injuries resulting from single bicycle crashes which are not recorded in road trauma surveillance systems based on police crash reports. This study aimed to examine the profile and circumstances of cycling injuries seen in an urban emergency department (ED). Methods: This was a cross-sectional historical chart review study. All injured patients attending our ED are electronically flagged according to mechanism of injury. We reviewed the medical charts of all ED visits in 2015 that were flagged as “Cyclist Injury” or “Fall” to identify all cyclists who were injured while travelling on public roads (including sidewalks). Off road injuries were excluded. Results: In 2015, a total of 6450 ED presentations were flagged as cyclist injury (n=694) or fall (n=5756), and 667 cycling injuries met our inclusion criteria. Of these, 73 (11%) were admitted to hospital. The most common mechanisms of injury were fall from bicycle (51%), crash into stationary object (16%), and collisions with moving motor vehicles (25%). Potential contributing factors included alcohol or drug impairment (11%), road hazards (9%), avoidance manoeuvre (5%) and dooring (3%), although the cause of the crash was generally poorly documented in the medical charts. The most common injured body regions were upper extremity (55%) followed by head and neck (34%). Most injuries were abrasions/lacerations and fractures. Conclusion: Two thirds of cyclist injuries in this series were caused by single bicycle incidents, events not captured in official road trauma statistics which are based on police crash reports. The large majority of injured cyclists were treated and released from the ED. In most cases, the cause of the crash was poorly documented. This data highlights the limitations of using police crash reports or hospital admission records for road trauma surveillance and the significant knowledge gap in our understanding of causative factors leading to cycling injuries.

Introduction: Walking as a form of active transportation is promoted by health professions and environmentalists alike. While the health benefits are indisputable, active transportation is not without risk. Pedestrians are vulnerable road users who often suffer serious injuries especially when involved with collisions with motor-vehicles. While pedestrian injuries involving motor-vehicles are captured in road trauma surveillance systems based on police crash reports, non-collision injuries in this population may be caused by poorly designed infrastructure but are seldom counted as road trauma. This gap hinders road improvement efforts aiming to increase safety for all road users. This study aims to address this knowledge gap. Our objective is to study the profile and circumstances of injuries in pedestrians presenting to ED. Methods: This was a cross-sectional historical chart review study. All injured patients attending our ED are electronically flagged according to mechanism of injury. We reviewed the medical charts of all ED visits flagged as “Pedestrian” or “Fall” to identify all injured pedestrians (defined in this study as anyone walking on a public roadway or getting on/off public transportation). All pedestrian injuries occurred in 2015 were included for chart review. Results: In 2015, a total of 6192 ED presentations were flagged as pedestrian (n=436) or fall (n=5756), and 1108 of these met our inclusion criteria. Of these, 181 (16%) were admitted to hospital. Older pedestrians (≥70 yrs) had a higher hospital admission rate (78/303; 27%) compared to younger ones (<70 yrs: 103/805; 13%). Collision with motor vehicles (MVCs) resulted in only 25% of pedestrian injuries while fall (or tripping) accounted for about 72%. MVC related injuries were more common in younger pedestrians (29% vs 13%) whereas fall related injuries occurred more in older pedestrians (85% vs 67%). The most commonly sustained injuries among the fallers were abrasions followed by fractures. Conclusion: Police crash reports (which capture only MVC related pedestrian injuries) or hospital admission data (which miss those who are treated and released from ED) do not capture all cases of pedestrian injury. ED visit data provides a more realistic count of pedestrian injuries. More pedestrian injuries are caused by falls than by MVCs and policymakers should pay more attention to fall prevention strategies for older pedestrians outside their home environment.

The aerodynamic performance of a multi-element high-lift system has a critical influence on the direct operating cost of a subsonic civil transport aircraft. A thorough understanding of the aerodynamic characteristics of these multi-element aerofoils and wings allows aircraft companies to design and build more competitive aircraft with high-lift systems that are less complex and lighter for given high-lift performance or that have improved lift and drag characteristics for given system complexity and weight. Flight experiments on NASA Langley's B737-100 aircraft have been conducted to further enhance the understanding of the complex flows about multi-element high-lift systems at full-scale flight conditions. In this paper, an overview of the flight program is provided, followed by highlights of experimental results and computational analysis. Measurements included surface pressures on the slats, main element and flap elements using flush pressure ports and pressure belts, surface shear stresses using Preston tubes, off-surface velocity distributions using boundary layer/wake rakes, aeroelastic deformations of the flap elements using an optical positioning system, and boundary layer transition detection using hot-film anemometers and an infrared imaging system. Boundary layer transition measurements on the slat using hot-film sensors are correlated with the flow visualisation results from an infrared imaging technique. Extensive application of several computational techniques and comparisons with flight measurements are shown for a limited number of cases. This program has generated an extensive set of data, much of which are still being analysed.

Infectious diseases establish in a population of wildlife hosts when the number of secondary infections is greater than or equal to one. To estimate whether establishment will occur requires extensive experience or a mathematical model of disease dynamics and estimates of the parameters of the disease model. The latter approach is explored here. Methods for estimating key model parameters, the transmission coefficient (β) and the basic reproductive rate (RDRS), are described using classical swine fever (hog cholera) in wild pigs as an example. The tentative results indicate that an acute infection of classical swine fever will establish in a small population of wild pigs. Data required for estimation of disease transmission rates are reviewed and sources of bias and alternative methods discussed. A comprehensive evaluation of the biases and efficiencies of the methods is needed.

Somatic cell nuclear transfer (SCNT) is not successful so far in non-human primates. The objective of this study was to investigate the effects of stimulation cycles (first and repeat) on oocyte retrieval and in vitro maturation (IVM) and to evaluate the effects of stimulation cycles and donor cell type (cumulus and fetal skin fibroblasts) on efficiency of SCNT with transported IVM oocytes. In this study, 369 immature oocytes were collected laparoscopically at 24 h following human chorionic gonadotrophin (hCG) treatment from 12 cynomolgus macaque (Macaca fascicularis) in 24 stimulation cycles, and shipped in pre-equilibrated IVM medium for a 5 h journey, placed in a dry portable incubator (37 °C) without CO2 supplement. A total of 70.6% (247/350) of immature oocytes reached metaphase II (MII) stage at 36 h after hCG administration, MII spindle could be seen clearly in 80.6% (104/129) of matured IVM oocytes under polarized microscopy. A total of 50.0% (37/74) of reconstructive SCNT embryos cleaved after activation; after cleavage, 37.8% (14/37) developed to the 8-cell stage and 8.1% (3/37) developed to morula, but unfortunately none developed to the blastocyst stage. Many more oocytes could be retrieved per cycle from monkeys in the first cycle than in repeated cycles (19.1 vs. 11.7, p < 0.05). There were no significant differences in the maturation rate (70.0 vs. 71.4%, p > 0.05) and MII spindle rate under polarized microscopy (76.4 vs. 86.0%, p > 0.05) between the first and repeat cycles. There were also no significant differences in the cleavage rate, and the 4-cell, 8-cell and morula development rate of SCNT embryos between the first and repeat cycles. When fibroblast cells and cumulus cells were used as the donor cells for SCNT, first cleavage rate was not significantly different, but 4-cell (50.0 vs. 88.9%, p < 0.05) and 8-cell (0 vs. 51.9%, p < 0.01) development rate were significantly lower for the former. In conclusion, the number of stimulation cycles has a significant effect on oocyte retrieval, but has no effect on maturation and SCNT embryo development; however, different donor cell types (cumulus and fibroblast) resulted in different developmental potentials of SCNT embryos.

Acute lung injury is defined as a syndrome of inflammation resulting in increased capillary-alveolar permeability that is associated with a constellation of clinical, radiological and physiological abnormalities. Adult respiratory distress syndrome (ARDS), relatively common in the intensive care, is a more specific, severe form of ALI, with diverse causes. Diffuse alveolar damage is the pathognomonic feature of the syndrome. Under the pathophysiologic conditions of increasing capillary membrane permeability, large macromolecules can gain access to the interstitium, resulting in pulmonary interstitial edema, and from there enter the alveolar space in severe cases. Detecting the distribution of macromolecules in lung tissue, therefore, constitutes evidence of the injury. Traditional pathologic examination of biopsy/autopsy materials is the only route to provide pathologic evidence of the capillary-alveolar membrane damage induced lung injury. Although morphometric analyses are more laborious, they provide qualitative assessment of morphological changes that is an important aspect of acute lung injury, see Fig.l.