The safety and accuracy of intratumoral catheter placement to infuse viral immunotherapies in children with malignant brain tumors: a multi-institutional study.

OBJECTIVE: Relatively little is known about the safety and accuracy of catheter placement for oncolytic viral therapy in children with malignant brain tumors. Accordingly, this study combines data from two phase I clinical trials that employed viral immunotherapy across two institutions to describe the adverse event profile, safety, and accuracy associated with the stereotactic placement and subsequent removal of intratumoral catheters. METHODS: Children with progressive/recurrent supratentorial malignant tumors were enrolled in two clinical trials (NCT03043391 and NCT02457845) and treated with either the recombinant polio:rhinovirus (lerapolturev) or the genetically modified oncolytic herpesvirus (G207). Age, sex, race, tumor diagnosis, and tumor location were analyzed. Events related to the catheter placement or removal were categorized. A catheter that was either pulled back or could not be used was defined as "misplaced." Neuronavigation software was used to analyze the accuracy of catheter placement for NCT03043391. Descriptive statistics were performed. RESULTS: Nineteen patients were treated across the two completed trials with a total of 49 catheters. The mean ± SD (range) age was 14.1 ± 3.6 (7-19) years. All tumors were grade 3 or 4 gliomas. Nonlobar catheter tip placement included the corpus callosum, thalamus, insula, and cingulate gyrus. Six of 19 patients (31.6%) had minor hemorrhage noted on CT; however, no patients were symptomatic and/or required intervention related to these findings. One of 19 patients had a delayed CSF leak after catheter removal that required oversewing of the surgical site. No patients developed infection or a neurological deficit. In 7 patients with accuracy data, the mean ± SD distance of the planned trajectory (PT) to the catheter tip was 1.57 ± 1.6 mm, the mean angle of the PT to the catheter was 2.43° ± 2.1°, and the greatest distance of PT to the catheter in the parallel plane was 1.54 ± 1.5 mm. Three of 49 (6.1%) catheters were considered misplaced. CONCLUSIONS: Although instances of minor hemorrhage were encountered, they were clinically asymptomatic. One of 49 catheters required intervention for a CSF leak. Congruent with previous studies in the literature, the stereotactic placement of catheters in these pediatric tumor patients was accurate with approximately 95% of catheters having been adequately placed.

Electrochemical C-F bond activation of trifluoromethylarenes using silylium ions.

We report a mild, electrochemical trihydrodefluorination (e-THDF) for breaking highly stable C-F bonds in trifluoromethyl arenes to form the corresponding methyl arene products. Uniquely, this "green" approach relies on the in situ generation of Lewis acidic silyl cations that mediate fluoride abstraction. Overall, e-THDF has significantly improved functional group tolerance over current methods and should inspire the continued development of defluorinative processes.

Correlates of bird collisions with buildings across three North American countries.

Collisions with buildings cause up to 1 billion bird fatalities annually in the United States and Canada. However, efforts to reduce collisions would benefit from studies conducted at large spatial scales across multiple study sites with standardized methods and consideration of species- and life-history-related variation and correlates of collisions. We addressed these research needs through coordinated collection of data on bird collisions with buildings at sites in the United States (35), Canada (3), and Mexico (2). We collected all carcasses and identified species. After removing records for unidentified carcasses, species lacking distribution-wide population estimates, and species with distributions overlapping fewer than 10 sites, we retained 269 carcasses of 64 species for analysis. We estimated collision vulnerability for 40 bird species with ≥2 fatalities based on their North American population abundance, distribution overlap in study sites, and sampling effort. Of 10 species we identified as most vulnerable to collisions, some have been identified previously (e.g., Black-throated Blue Warbler [Setophaga caerulescens]), whereas others emerged for the first time (e.g., White-breasted Nuthatch [Sitta carolinensis]), possibly because we used a more standardized sampling approach than past studies. Building size and glass area were positively associated with number of collisions for 5 of 8 species with enough observations to analyze independently. Vegetation around buildings influenced collisions for only 1 of those 8 species (Swainson's Thrush [Catharus ustulatus]). Life history predicted collisions; numbers of collisions were greatest for migratory, insectivorous, and woodland-inhabiting species. Our results provide new insight into the species most vulnerable to building collisions, making them potentially in greatest need of conservation attention to reduce collisions and into species- and life-history-related variation and correlates of building collisions, information that can help refine collision management.

Correlaciones de las Colisiones de Aves contra Edificios en Tres Países de América del Norte Resumen Las colisiones contra los edificios causan hasta mil millones de fatalidades de aves al año en los Estados Unidos y en Canadá. Sin embargo, los esfuerzos por reducir estas colisiones se beneficiarían con estudios realizados a grandes escalas espaciales en varios sitios de estudio con métodos estandarizados y considerando las variaciones relacionadas a la historia de vida y a la especie y las correlaciones de las colisiones. Abordamos estas necesidades de investigación por medio de una recolección coordinada de datos sobre las colisiones de aves contra edificios en los Estados Unidos (35), Canadá (3) y México (2). Recolectamos todos los cadáveres y los identificamos hasta especie. Después de retirar los registros de cadáveres no identificados, las especies sin estimaciones poblacionales a nivel distribución y las especies con distribuciones traslapadas en menos de diez sitios, nos quedamos con 269 cadáveres de 64 especies para el análisis. Estimamos la vulnerabilidad a colisiones para 40 especies con ≥2 fatalidades con base en la abundancia poblacional para América del Norte, el traslape de su distribución entre los sitios de estudio y el esfuerzo de muestreo. De las diez especies que identificamos como las más vulnerables a las colisiones, algunas han sido identificadas previamente (Setophaga caerulescens), y otras aparecieron por primera vez (Sitta carolinensis), posiblemente debido a que usamos una estrategia de muestreo más estandarizada que en los estudios previos. El tamaño del edificio y el área del vidrio estuvieron asociados positivamente con el número de colisiones para cinco de ocho especies con suficientes observaciones para ser analizadas independientemente. La vegetación alrededor de los edificios influyó sobre las colisiones solamente para una de esas ocho especies Catharus ustulatus). Las historias de vida pronosticaron las colisiones; el número de colisiones fue mayor para las especies migratorias, insectívoras y aquellas que habitan en las zonas boscosas. Nuestros resultados proporcionan una nueva perspectiva hacia las especies más vulnerables a las colisiones contra edificios, lo que las pone en una necesidad potencialmente mayor de atención conservacionista para reducir estas colisiones y de estudio de las variaciones relacionadas con la especie y la historia de vida y las correlaciones de las colisiones contra edificios, información que puede ayudar a refinar el manejo de colisiones.

Autograft-derived spinal cord mass in the cervical spine following transplantation with olfactory mucosa cells for traumatic spinal cord injury: case report.

This study describes a patient with an autograft-derived spinal cord mass following transplantation of olfactory mucosa for treatment of cervical spine injury. The authors report the case of a 35-year-old man who suffered a complete spinal cord injury (SCI) at C5-6 in 2001. The patient underwent an olfactory mucosal cell implantation at the location of injury 4 years following initial trauma. Twelve years later, the patient presented with rapidly progressive decline in upper-extremity function as well as neuropathic pain. Imaging revealed a heterogeneously enhancing intramedullary mass from C3 to C7. At surgery, the patient was found to have a posttransplant mucinous mass. Each mucinous cyst was drained and a portion of the cyst wall was removed. Histological examination demonstrated ciliated epithelium-lined fibrous tissue, submucosal glands, and mucoid material, consistent with a transplant-derived tumor. This case report both documents a rare long-term complication of olfactory mucosal cell transplantation and serves as a cautionary tale encouraging prudent use of novel treatments in a vulnerable population of patients with severe SCI.

MORBIDITY AND MORTALITY OF WILD TURTLES AT A NORTH CAROLINA WILDLIFE CLINIC: A 10-YEAR RETROSPECTIVE.

The medical records from 1,847 wild turtle patients seen between 2005 and 2014 by the Turtle Rescue Team at the North Carolina State University College of Veterinary Medicine were analyzed. Eastern box turtles (Terrapene carolina carolina; n = 947), yellow-bellied sliders (Trachemys scripta scripta; n = 301), cooters ( Pseudemys spp.; n = 235), common snapping turtles (Chelydra serpentina; n = 165), and eastern painted turtles (Chrysemys picta; n = 93) made up 94.3% of all patients. Patient admissions peaked in May when 25.6% (473/1,847) of all turtles were admitted. Cooters were the most-likely species to be gravid, and the loss of gravid females may put this population at increased risk for decline. The majority of wild turtles presented for anthropogenic causes, primarily vehicular trauma (63.2%; 1,168/1,847), which also had the greatest mortality at 57.8% (675/1,168) of any presenting complaint. Coelomic breach was the presenting injury with greatest risk of dying, increasing the risk of dying by 4.8 times. Other factors that were associated with increased mortality included head injuries, myiasis, and cranial or caudal midline injuries. Of all turtle species, eastern box turtles most commonly presented for nontraumatic conditions including aural abscesses (8.2%; 78/947), upper respiratory infections (6.3%; 60/947), and both conditions concurrently (2.5%; 14/947). While many turtles presented with little to no chance for survival in the wild, 47.6% were eventually released and that number increased to 62.0% released for those that survived 24 hr or longer after presentation. This study adds to the knowledge about the treatment of injured and diseased wild turtles in order to potentially ameliorate the overall impact of humans, especially as a result of vehicular trauma.

Accuracy of Novel Computed Tomography-Guided Frameless Stereotactic Drilling and Catheter System in Human Cadavers.

OBJECTIVE: To evaluate accuracy of a computed tomography (CT)-guided frameless stereotactic drilling and catheter system. METHODS: A prospective, single-arm study was performed using human cadaver heads to evaluate placement accuracy of a novel, flexible intracranial catheter and stabilizing bone anchor system and drill kit. There were 20 catheter placements included in the analysis. The primary endpoint was accuracy of catheter tip location on intraoperative CT. Secondary endpoints included target registration error and entry and target point error before and after drilling. Measurements are reported as mean ± SD (median, range). RESULTS: Target registration error was 0.46 mm ± 0.26 (0.50 mm, -1.00 to 1.00 mm). Two (10%) target point trajectories were negatively impacted by drilling. Intracranial catheter depth was 59.8 mm ± 9.4 (60.5 mm, 38.0-80.0 mm). Drilling angle was 22° ± 9 (21°, 7°-45°). Deviation between planned and actual entry point on CT was 1.04 mm ± 0.38 (1.00 mm, 0.40-2.00 mm). Deviation between planned and actual target point on CT was 1.60 mm ± 0.98 (1.40 mm, 0.40-4.00 mm). No correlation was observed between intracranial catheter depth and target point deviation (accuracy) (Pearson coefficient 0.018) or between technician experience and accuracy (Pearson coefficient 0.020). There was no significant difference in accuracy with trajectories performed for different cadaver heads (P = 0.362). CONCLUSIONS: Highly accurate catheter placement is achievable using this novel flexible catheter and bone anchor system placed via frameless stereotaxy, with an average deviation between planned and actual target point of 1.60 mm ± 0.98 (1.40 mm, 0.40-4.00 mm).

Impact of Education on School-aged Children's Knowledge of and Participation in "The Choking Game".

OBJECTIVES: To better understand school-aged children's awareness of and attitudes about the Choking Game (TCG). To determine if education can increase awareness of the risk of injury when playing TCG and to determine if education can decrease interest in TCG participation. DESIGN: Anonymous pre- and post-education surveys. SETTING: Two middle/high schools; one in Utah and one in California. SUBJECTS: 291 participants (163 in Utah, 128 in California) aged 9-18, 68% under age 15, 32% 15 and older; 65% white, 35% non-white; 52% female, 48% male. RESULTS: 76% of participants knew about TCG, of those 62% heard about it at school. 32% knew someone who had played, and twelve (4%) had played, usually with others. Most frequently cited as reasons for participation were curiosity, peer pressure, and competition. School was the most common location for playing. In California education significantly increased risk awareness, and significant positive attitude changes were observed regarding interest in playing TCG. Utah participants also exhibited attitude changes in the desired direction (less interest in playing TCG, would warn friends, and realized it was not safe to stop breathing), although results were not statistically significant, possibly due to previous education and four recent and highly publicized TCG deaths in the community. CONCLUSION: Results indicate that interactive, standardized, and skills-based education can increase student awareness of TCG risks and decrease interest in participation. Students reported that the schools were often where they first heard about TCG and where TCG was commonly played. Educators and associated health care professionals should therefore be encouraged to provide preventative education as part of school curricula.

Quantitative cancer risk assessment for occupational exposures to asphalt fumes during built-up roofing asphalt (BURA) operations.

The International Agency for Research on Cancer qualitatively characterized occupational exposure to oxidized bitumen emissions during roofing as probably carcinogenic to humans (Group 2A). We examine chemistry, exposure, epidemiology and animal toxicity data to explore quantitative risks for roofing workers applying built-up roofing asphalt (BURA). Epidemiology studies do not consistently report elevated risks, and generally do not have sufficient exposure information or adequately control for confounders, precluding their use for dose-response analysis. Dermal carcinogenicity bioassays using mice report increased tumor incidence with single high doses. In order to quantify potential cancer risks, we develop time-to-tumor model methods [consistent with U.S. Environmental Protection Agency (EPA) dose-response analysis and mixtures guidelines] using the dose-time-response shape of concurrent exposures to benzo[a]pyrene (B[a]P) as concurrent controls (which had several exposure levels) to infer presumed parallel dose-time-response curves for BURA-fume condensate. We compare EPA relative potency factor approaches, based on observed relative potency of BURA to B[a]P in similar experiments, and direct observation of the inferred BURA dose-time-response (scaled to humans) as means for characterizing a dermal unit risk factor. We apply similar approaches to limited data on asphalt-fume inhalation and respiratory cancers in rats. We also develop a method for adjusting potency estimates for asphalts that vary in composition using measured fluorescence. Overall, the various methods indicate that cancer risks to roofers from both dermal and inhalation exposure to BURA are within a range typically deemed acceptable within regulatory frameworks. The approaches developed may be useful in assessing carcinogenic potency of other complex mixtures of polycyclic aromatic compounds.

Intrinsically disordered N-terminus of calponin homology-associated smooth muscle protein (CHASM) interacts with the calponin homology domain to enable tropomyosin binding.

The calponin homology-associated smooth muscle (CHASM) protein plays an important adaptive role in smooth and skeletal muscle contraction. CHASM is associated with increased muscle contractility and can be localized to the contractile thin filament via its binding interaction with tropomyosin. We sought to define the structural basis for the interaction of CHASM with smooth muscle tropomyosin as a first step to understanding the contribution of CHASM to the contractile capacity of smooth muscle. Herein, we provide a structure-based model for the tropomyosin-binding domain of CHASM using a combination of hydrogen/deuterium exchange mass spectrometry (HDX-MS) and NMR analyses. Our studies provide evidence that a portion of the N-terminal intrinsically disordered region forms intramolecular contacts with the globular C-terminal calponin homology (CH) domain. Ultimately, cooperativeness between these structurally dissimilar regions is required for CHASM binding to smooth muscle tropomyosin. Furthermore, it appears that the type-2 CH domain of CHASM is required for tropomyosin binding and presents a novel function for this protein domain.