Abstract

The body armor of ankylosaurians is a unique morphological feature among dinosaurs. While ankylosaurian body armor has been studied for decades, paleohistological analyses have only started to uncover the details of its function. Yet there has been an overall bias toward sampling ankylosaurian remains from the Northern Hemisphere, with limited quantitative studies on the morphological and functional evolution of the osteoderms composing their body armor. Here, we describe new ankylosaurian materials recovered from the Late Cretaceous of Antarctica that, in combination with data compiled from the literature, reveal new insights into the evolution of the ankylosaurian body armor. Based on histological microstructure and phylogenetic results, the new Antarctic material can be assigned to Nodosauridae. This group shares the absence/poor development of their osteodermal basal cortex and highly ordered sets of orthogonal structural fibers in the superficial cortex. Our morphospace analyses indicate that large morphological diversity is observed among both nodosaurids and ankylosaurids, but osteoderms became more functionally specialized in late-diverging nodosaurids. Besides acting as effective protection against predation, osteoderms also exhibit highly ordered structural fibers in nodosaurids, enabling a decrease in cortical bone thickness (as in titanosaurs), which could have been co-opted for secondary functions, such as calcium remobilization for physiological balance. The latter may have played a key role in nodosaurid colonization of high-latitude environments, such as Antarctica and the Arctic Circle.

Background: Tuberous Sclerosis Complex (TSC) is a genetic disease that affects multiple body systems with the neurological manifestations causing the greatest disease burden. The objective of this study was to understand the scope of neurological TSC care delivery across Canada. Methods: A survey was developed after literature review and discussion amongst two Paediatric Epileptologists and one Nurse Practitioner with expertise in TSC. Canadian Paediatric Neurologists participated via an anonymous web-based survey through the Canadian League Against Epilepsy (CLAE) and Canadian Neurological Sciences Federation (CNSF). Results: Fifty-eight responses were received. A dedicated TSC clinic was reported by 24% (n=14). Sixty percent (n= 35) reported preforming serial screening EEG monitoring in infants and 58% (n= 34) started prophylactic therapy when EEG abnormalities occurred. Vigabatrin was used in 37% (n=21). For management of drug-resistant epilepsy, surgery was reported as the preferred therapeutic option in 57% (n=32) of respondents. Barriers to treatment identified were a lack of multi-disciplinary care, unfamiliarity with new therapies and insufficient resources. Conclusions: Our findings demonstrate the variability in neurological care delivery of patients with TSC. With few dedicated TSC clinics, there is a need for the establishment of a national network to support clinical practice, research and education.

Background: Infantile spasms (IS) is an epileptic encephalopathy, characterized by spasms, hypsarrhythmia, and developmental regression. This is a retrospective case series of children with IS who underwent epilepsy surgery at The Hospital for Sick Children (HSC) in Toronto, Canada. Methods: The records of 223 patients seen in the IS clinic were reviewed. Results: Nineteen patients met inclusion criteria. The etiology of IS was encephalomalacia in six patients (32%), malformations of cortical development in 11 patients (58%), atypical hypoglycaemic injury in one patient (5%), and partial hemimegalencephaly in one patient (5%). Nine patients (47%) underwent hemispherectomy and 10 patients (53%) underwent lobectomy/lesionectomy. Three patients (16%) underwent a second epilepsy surgery. Fifteen patients (79%) were considered ILAE Seizure Outcome Class 1 (completely seizure free; no auras). The percentage of patients who were ILAE Class 1 at most recent follow-up decreased with increasing duration of epilepsy prior to surgery. Developmental outcome was improved in 14/19 (74%) and stable in 5/19 (26%) patients. Conclusions: Our study found excellent seizure freedom rates and improved developmental outcomes following epilepsy surgery in patients with a history of IS with a structural lesion detected on MRI brain.

Background: We aimed to study the proportion of patients with DRE and pre-existing VNS device, who show improvement of at least one class in McHugh seizure outcome classification at last follow up after generator replacement with cardiac based VNS device. Methods: We retrospectively reviewed children with DRE with the older VNS model (102) who underwent battery replacement with the AspireSR®, model 106 since September 2016 at our institution. We assessed the seizure outcomes since the first VNS device insertion till the last follow up after AspireSR® (with cardiac-based seizure detection) using McHugh seizure outcome classification. Results: The study population was comprised of 15 patients. The mean age at seizure onset was 2.7 years old, with mean age of initial VNS1 placement being 10.1 years and mean age of replacement with VNS2 being 14.9 years of age. Three of the fifteen patients had reported status epilepticus prior to initial VNS insertion, and none reported episodes following insertion. Two patients showed at least one class improvement in McHugh seizure outcomes at last follow up after VNS2. Conclusions: Through our preliminary data at the present time, we note that the majority of our patients maintains their seizure control following replacement with VNS2 with a few showing improvement.

Background: Infantile spasms (IS) is an epileptic encephalopathy, characterized by epileptic spasms, hypsarrhythmia, and developmental regression. This is a retrospective case series detailing the experience in children with IS who have undergone epilepsy surgery at The Hospital for Sick Children (HSC). Methods: Records of 223 patients from HSC were reviewed. Patients were included if they had a current or previous history of IS with a lesion detected on MRI/PET scan who underwent epilepsy surgery. Results: Nineteen patients were included. The etiology of IS was encephalomalacia in six patients (32%), malformations of cortical development in 11 patients (58%), atypical hypoglycaemic injury in one patient (0.5%), and partial hemimegalencephaly in one patient (0.5%). The median age at the onset of IS was five months. The median age at surgery was 18 months. Nine patients (47%) underwent hemispherectomy and 10 patients (53%) underwent lobectomy/lesionectomy. Fifteen patients (79%) were considered ILAE Seizure Outcome Class 1. Developmental outcome was improved in 14/19 (74%) and stable in 5/19 (26%) patients. Conclusions: Even with a generalized EEG pattern such as hypsarrhythmia, patients should be considered for focal resective surgery. Early surgical intervention shortens the duration of active epilepsy thus limiting the potentially irreversible effects of on-going seizures.

Developing and improving an antimicrobial stewardship program successfully requires evaluation of numerous factors. As technology progresses and our understanding of antimicrobial resistance grows, careful consideration should be taken to ensure that a program meets the needs of the institution and is achievable given the available resources. In this review, we explore fundamental initiatives and strategies for both new and established antimicrobial stewardship programs, including the specific areas to target and key elements required for sustainable implementation.

Cyclosporiasis is an illness characterised by watery diarrhoea caused by the food-borne parasite Cyclospora cayetanensis. The increase in annual US cyclosporiasis cases led public health agencies to develop genotyping tools that aid outbreak investigations. A team at the Centers for Disease Control and Prevention (CDC) developed a system based on deep amplicon sequencing and machine learning, for detecting genetically-related clusters of cyclosporiasis to aid epidemiologic investigations. An evaluation of this system during 2018 supported its robustness, indicating that it possessed sufficient utility to warrant further evaluation. However, the earliest version of CDC's system had some limitations from a bioinformatics standpoint. Namely, reliance on proprietary software, the inability to detect novel haplotypes and absence of a strategy to select an appropriate number of discrete genetic clusters would limit the system's future deployment potential. We recently introduced several improvements that address these limitations and the aim of this study was to reassess the system's performance to ensure that the changes introduced had no observable negative impacts. Comparison of epidemiologically-defined cyclosporiasis clusters from 2019 to analogous genetic clusters detected using CDC's improved system reaffirmed its excellent sensitivity (90%) and specificity (99%), and confirmed its high discriminatory power. This C. cayetanensis genotyping system is robust and with ongoing improvement will form the basis of a US-wide C. cayetanensis genotyping network for clinical specimens.

Clinical research coordinators are increasingly tasked with a multitude of complex study activities critical to scientific rigor and participant safety, though more than half report not receiving appropriate training. To determine the reproducibility of an established clinical research workforce orientation program, collaborative partners across Clinical and Translational Science Award institutions seeded core principles and structure from Mayo Clinic’s Clinical Research Orientation program within Penn State University and the University of Mississippi Medical Center from 2019 to 2021. Training concepts were established and tied to those domains deemed critical by the Joint Task Force for Clinical Trial Competency for the conduct of clinical research at the highest levels of safety and quality possible. Significant knowledge and confidence gains and high overall program satisfaction were reported across participants and partner sites, despite programs being required to pivot from traditional, in-person formats to entirely virtual platforms as a result of the COVID-19 pandemic. The successful standardization and translation of foundational clinical research training has important efficiency and efficacy implications for research enterprises across the USA.

In a survey of adult hospital providers regarding antibiotic use in the treatment of febrile neutropenia, clinical fellows, and pharmacists showed higher comfort levels with early antimicrobial de-escalation compared to hematology-oncology and transplant infectious diseases physicians. These frontline team members are ideal partners to champion antimicrobial stewardship interventions in febrile neutropenia.

Foodborne salmonellosis causes approximately 1 million illnesses annually in the United States. In the summer of 2017, we investigated four multistate outbreaks of Salmonella infections associated with Maradol papayas imported from four Mexican farms. PulseNet initially identified a cluster of Salmonella Kiambu infections in June 2017, and early interviews identified papayas as an exposure of interest. Investigators from Maryland, Virginia and Food and Drug Administration (FDA) collected papayas for testing. Several strains of Salmonella were isolated from papayas sourced from Mexican Farm A, including Salmonella Agona, Gaminara, Kiambu, Thompson and Senftenberg. Traceback from two points of service associated with illness sub-clusters in two states identified Farm A as a common source of papayas, and three voluntary recalls of Farm A papayas were issued. FDA sampling isolated four additional Salmonella strains from papayas sourced from Mexican Farms B, C and D. In total, four outbreaks were identified, resulting in 244 cases with illness onset dates from 20 December 2016 to 20 September 2017. The sampling of papayas and the collaborative work of investigative partners were instrumental in identifying the source of these outbreaks and preventing additional illnesses. Evaluating epidemiological, laboratory and traceback evidence together during investigations is critical to solving and stopping outbreaks.

Background: Continuous electroencephalographic (cEEG) monitoring is essential to diagnosing non-convulsive seizures (NCS), reported to occur in 7-46% of at-risk critically ill patients. However, cEEG is labour-intensive, and given scarcity of resources at most centres cEEG is feasible in only selected patients. We aim to evaluate the clinical utility of cEEG at our centre in order to optimize further cEEG allocation among critically ill patients. Methods: Using a clinical database, we identified critically ill children who underwent cEEG monitoring in 2016, 2017 and 2018. We abstracted underlying diagnoses, indication for cEEG monitoring, cEEG findings, and associated changes in management. Results: Over this three year period, 928 cEEGs were performed. Among the 100 studies analyzed to date, primary indications for monitoring were characterization of events of unclear etiology (32%), diagnosis of NCS (30%), and monitoring of therapy for seizures (17%). Seizures were captured in 31% of patients (22% subclinical only, 5% electroclinical only, 4% both), which resulted in a treatment change in 90% of cases. Non-epileptic events were captured in 26% of patients. Conclusions: cEEG yielded clinically meaningful information in 57% of cases, frequently resulting in management changes. Subgroup analyses by cEEG indication and ICU location will be presented.

It is known that tungsten oxide may be reacted with selenium sources to form WSe2 but literature reports include processing steps that involve high temperatures, reducing atmospheres, and/or oxidative pre-treatments of tungsten oxide. In this work, we report a non-vacuum process for the fabrication of compositionally high quality WSe2 thin films via the selenization of tungsten oxide under milder conditions. Tungsten source materials were various hydrated WO3 and WO2.9 compounds that were prepared using chemical solution techniques. Resulting films were selenized using a two-stage heating profile (250 °C for 15 minutes and 550 °C for 30 minutes) under a static argon atmosphere. Effects of the starting tungsten oxide phase on WSe2 formation after single and double selenization cycles were investigated using Raman spectroscopy and X-ray diffraction (XRD). After two selenization cycles, hydrated WO3 was converted to (002)-oriented WSe2 that exhibits well-resolved peaks for E12g and A1g phonon modes. Only a single selenization cycle was required to convert amorphous WO2.9 to WSe2. All selenizations in this work were achieved in non-reducing atmospheres and at lower temperatures and shorter times than any non-laser-assisted processes reported for WO3-to-WSe2 conversions.

Diurnal preference (e.g., being an owl or lark) has been associated with several psychiatric disorders including bipolar disorder (BP), major depressive disorder, and substance use disorders. Previous large-scale genome-wide association studies (GWAS) aimed at identifying genetic influences on diurnal preference have exclusively included subjects of European ancestry. This study examined the genetic architecture of diurnal preference in two minority samples: a young adult sample of Mexican Americans (MAs), and a family-based sample of American Indians (AIs). Typed or imputed variants from exome chip data from the MA sample and low pass whole-genome sequencing from the AI cohort were analyzed using a mixed linear model approach for association with being an owl, as defined by a usual bedtime after 23:00 hrs. Genetic risk score (GRS) profiling detected shared genetic risk between evening preference and related disorders. Four variants in KIAA1549 like (KIAA1549L), a gene previously associated with attempted suicide in bipolar patients, were suggestively associated with being an owl at p < 1.82E-05; post hoc analyses showed the top variant trending in both the MA and AI cohorts at p = 2.50E-05 and p = .030, respectively. Variants associated with BP at p < .03 from the Psychiatric Genomics Consortium nominally predicted being an owl in the MA/AI cohort at p = .012. This study provides some additional evidence that genetic risk factors for BP also confer risk for being an owl in MAs/AIs and that evening preference may be a useful endophenotype for future studies of BP.

A submerged delta of the Merrimack River, located offshore between Cape Ann, Massachusetts, and the New Hampshire border, indicates a postglacial low relative see-level stand of about −47 m. The low stand is inferred to date to 10,500 yr B.P., but a lack of age control makes this assignment uncertain. A curve based on a late Wisconsinan, high relative sea-level stand of +32m at 13,000 yr B.P., a low stand of −47m at 10,500 yr B.P., and younger radiocarbon dates related to sea-level rise indicates an early postglacial crustal rise of at least 5 m per century.