Excessive breeding for brachycephaly (fore-shortened muzzle) has led to increasing problems in pugs related to brachycephalic airway syndrome (BAS). Consequently, the German Pug Club (Deutscher Mopsclub eV; DMC) established a stress test in 2009 that must be passed for breeding and requires normalised heart and respiratory rates 15 min after having covered a distance of 1 km. In this study, 42 pugs underwent the stress test under standardised conditions. Taking into account that this exercise should not be too physically demanding for any healthy dog, the results were surprising: 14 of the pugs failed, ie a failure rate of 33.3%. In addition to the stress test, the pugs were assessed according to their heart and respiratory rates at rest, which we predicted would be associated with BAS, and in this test, 21 out of 42 pugs failed. Thus, 50.0% of the pugs were in a severely compromised physical condition. A further group of seven retropugs, ie a crossbreed of pugs with a slightly longer muzzle, was included in the study to compare brachycephalic problems. All of the retropugs passed the test, even when respiratory and heart rates at rest were considered. However, the findings may not be transferable to all retropugs because of the small sample size, so further research is needed. In summary, this study has enabled the development of recommendations for future implementation of stress tests.

Introduction: Participation in Global Health (GH) electives can improve resourcefulness, cultural and ethical insight, and personal development. Risks to trainees, hosts and institutions may be minimized through pre-departure and post-elective training. In 2016 such training was mandatory in only 3 Canadian residency programs, however there is no published data specific to Canadian Emergency Medicine (EM) programs. This study sought to identify current GH elective requirements and related perceived gaps among Royal College EM programs. Methods: We conducted two cross-sectional surveys in 2019 (one each for Royal College EM PDs and residents) via email regarding training requirements for GH electives. Additionally, a survey link was distributed in the CAEP EM resident newsletter. We also contacted university PGME and/or global health offices to understand and collate university-wide requirements and resources. Results: Nine PDs responded, with 78% reporting having 1-5 residents participate in GH electives yearly. Many PDs were unsure of the requirements surrounding GH electives; two reported that pre-departure training was required, while none reported requiring post-departure debriefs. Overall, 67% of PDs felt that their residents were moderately prepared for GH electives and 33% felt they were unprepared to some degree. Thirty-three percent believed that improvements should be made to either pre-departure training or both pre- and post-departure training, while 56% were unsure if improvements were needed. Forty-seven out of an estimated 380 residents responded. Thirty-five percent of residents had completed a GH elective during residency. Of residents who participated in a GH elective, only one (6%) reported feeling very prepared; 18 residents (43%) reported there was a need to improve trainings. Residents reported a number of challenges during electives (lack of resources, inadequate supervision, safety issues) and identified priority topics for training. Conclusion: Although EM residents are participating in GH electives, the majority of EM residency programs do not require pre- or post-departure training. Some PDs and residents report varying levels of preparedness, and residents acknowledge a variety of challenges during GH electives. This information can be used to inform pre-departure/post-elective GH training or to encourage EM residents to access university-wide training.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.

Molecular characterization of pediatric low-grade glioma (pLGG) over the last decade has identified recurrent alterations, most commonly involving BRAF, and less frequently other pathways including MYB and MYBL1. Many of these molecular markers have been exploited clinically to aid in diagnosis and treatment decisions. However, their frequency and prognostic significance remain unknown. Further, a significant portion of cases do not have any of these alterations and what underlies these cases remains unknown. To address this we compiled a cohort of 562 patients diagnosed at SickKids from 1990-2017. We identified molecular alterations in 454 cases (81% of the cohort). The most frequent events were those involving BRAF; either as fusions (most commonly with KIAA1549 (30%)) or V600E mutations (17%) and NF-1 (22%). Less frequently, we identified recurrent FGFR1 fusions and mutations (3%), MYB/MYBL alterations (2%), H3F3AK27M (2%) or IDH1R132H (0.5%) mutations, as well as other novel rare events. Survival analysis revealed significantly better progression-free survival (PFS) and overall survival (OS) of KIAA1549-BRAF fused patients compared to BRAFV600E with 10-year OS 97.7% (95%, CI 95.5-100) and 83.9% (95%, CI 72.5-95.6), respectively. In addition to survival, molecular alterations predicted differences in response to conventional therapeutics; BRAF fused patients showed a 46% response-rate, versus only 14% in V600E patients. pLGGs harboring H3F3AK27M progressed early with median PFS of 11 months. In patients with MYB/MYBL1, FGFR1/FGFR2 alterations, we observed only one death (FGFR1N546K case). The work here represents the largest cohort of pLGGs with molecular profiling and their impact on the clinical behaviour of the disease.

Introduction: It is critical for planning, clinical care and resource optimization to understand patterns of emergency department (ED) utilization. Individuals who have experienced adverse childhood experiences (ACE) are known to have more unhealthy behaviors and worse health outcomes as adults and therefore may be more frequent ED users. Adverse childhood experiences include physical, sexual and emotional abuse or neglect, substance abuse in the family, witnessing violence, having a parent incarcerated or parents getting divorced or separated. To date there are few studies exploring the relationship between ACE and ED utilization. Methods: This a mixed qualitative and quantitative study. It includes analysis of data collected through a survey, a retrospective chart review and focus group discussions. The survey was administered to a convenience sample of adult patients (CTAS 2 -5) presenting to EDs in Kingston Ontario, and consisted of two validated tools that measured exposure to ACE and resiliency. Demographic data and ED utilization frequency for 12 months prior to the index visit were extracted from an electronic medical record for each patient completing the survey. A sample of participants with a high ACE burden (ACE score > 4) were invited to participate in focus groups to explore their experiences of care in the ED. Demographic, ED utilization and health status data were summarized and statistically significant patterns between high ACE and lower ACE patients were determined using Chi2t or t-tests. Transcripts from the focus groups were thematically analyzed using NVivo software by 2 independent researchers. Results: 1693 surveys were collected, 301 (18%) were deemed to have a high ACE score, data analysis is ongoing. The primary outcome is the relationship between ACE and the frequency of ED utilization among adult patients presenting to EDs in Kingston, ON. Secondary outcomes include evaluating the role of resilience as a potential mitigating factor, describing the demographics of high ACE burden frequent ED visitors, and the experiences of care for individuals with high ACE burden in the ED. These outcomes will be utilized to inform hypotheses for future studies and potential interventions aimed at optimizing ED utilization and patient care experience. Conclusion: This study provides novel insight into the relationship between ACE burden and ED utilization while also describing the demographics and experiences of care for ED patients with a high ACE score. Data analysis is on-going.

Introduction: Global Emergency Medicine (Global EM) is growing rapidly as an academic niche in Canada. An increasing number of Canadian emergency physicians work internationally as part of their practice, and trainees consistently seek out international projects and electives. For the most part however, residents have had to create their own training opportunities as formal Global EM fellowship training has been lacking in Canada. To address this identified need, Queens University established a Global EM fellowship, the first of its kind in the country. Methods: The fellowship is designed to provide the skills necessary for an academic career in Global Emergency Medicine. Curriculum and objectives are modeled on similar well-established fellowships in the United States. Areas of expertise include emergency medicine systems development, humanitarian medicine, disaster response, public health, tropical medicine, research, administration and education. Fellows have the opportunity to tailor their training according to their specific interests within these domains. Importantly, the fellowship provides direct mentorship from academic global EM and public health physicians, and networking opportunities within the global health sphere. Results: The two-year fellowship curriculum is divided between: 1) coursework to complete a Master of Public Health (MPH) Degree 2) fieldwork 3) relevant international emergency medicine training courses and 4) clinical work in the emergency departments at the Kingston Health Sciences Center. The Queens Global EM fellowship admitted its first fellow in August 2017. To date, the inaugural fellow has completed the MissionCraft Leadership in Disaster Relief course as well as a Humanitarian U Disaster and Response course, in addition to submitting a research grant as a co-principal investigator, starting coursework for an MPH degree and giving several invited lectures on humanitarian medicine. The fellow also travelled to Lebanon to support research in collaboration with aid organizations responding to the Syrian crisis. Upcoming fieldwork involves teaching at a newly established emergency medicine residency program in Haiti as well as a humanitarian crisis deployment. Conclusion: In response to a lack of formal international emergency medicine training opportunities in Canada, Queens University has established a Global Emergency Medicine fellowship. The fellowship aims to provide protected time, access to field opportunities and dedicated mentorship to develop the skills necessary to succeed as an academic Global EM physician. We believe it provides a unique opportunity to significantly expand fellows experiences in global health fieldwork, education and research while continuing to practice in a Canadian tertiary emergency department.

We present an indentation-scope that interfaces with confocal microscopy, enabling direct observation of the three-dimensional (3D) microstructural response of coatings on substrates. Using this method, we compared microns-thick polymer coatings on glass with and without silica nanoparticle filler. Bulk force data confirmed the >30% modulus difference, while microstructural data further revealed slip at the glass-coating interface. Filled coatings slipped more and about two times faster, as reflected in 3D displacement and von Mises strain fields. Overall, these data indicate that silica-doping of coatings can dramatically alter adhesion. Moreover, this method compliments existing theoretical and modeling approaches for studying indentation in layered systems.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

Inhibition of seedling growth and four assays for inhibition of photosynthesis were used to compare karbutilate [tert-butylcarbamic acid ester with 3-(m-hydroxyphenyl)-1,1-dimethylurea] with derivatives of karbutilate in which either the urea or carbamate side chain was missing. Karbutilate was a more potent, more presistent, and more specific inhibitor of photosynthesis than the phenylurea derivative fenuron (1,1-dimethyl-3-phenylurea) that would be formed by removal of the carbamate side chain. However, karbutilate did not exert the growth-inhibiting action observed for the alkyl carbamate derivative phenyl-N-tert-butylcarbamate, formed by removal of the urea side chain, which does not affect photosynthesis at concentrations below 10-3 M.

Fieldwork conducted in the Wasatch Formation in and around Fossil Butte has yielded a diverse assemblage of early Eocene vertebrates. Fossil vertebrates are distributed through three discrete stratigraphic intervals within the uppermost 180 m of the main body of the Wasatch Formation underlying the Green River Formation. These assemblages were derived primarily from fluvial overbank mudstone units overprinted with variably well-developed paleosols. The lowest (20 m) and highest (60 m) sections are characterized by less mature and more hydromorphic paleosols, whereas the middle section (100 m) is typified by more mature paleosols and more abundant channel sandstones.

The combined assemblages contain at least 46 species of mammals. Faunal characteristics include high abundances of equid perissodactyls and a relatively high abundance and diversity of notharctines primates, an apparent absence of omomyid primates, relatively high rodent diversity, and relatively diverse and abundant artiodactyls. One new genus (Eoictops new genus) and three new species (Eoictops novaceki new species, Palaeosinopa lacus new species, and ?Notoparamys blochi new species) are included in the Fossil Butte assemblage. Also recorded are late occurrences of two hyopsodontid condylarths and an early occurrence of a rare phenacodontid condylarth. The relatively high abundances of equids and notharctines suggest that vertebrate samples were derived from relatively open paleohabitats that included forested areas along water courses.

All three assemblages contain characteristic Lysitean (Wasatchian biochron Wa-6) elements, but the occurrence of the palaeotheriid perissodactyl Lambdotherium in the uppermost horizon indicates a Lostcabinian (Wa-7) age for at least the top of the Wasatch Formation. The overlying predominantly fish-bearing Fossil Butte Member of the Green River Formation also contains Lambdotherium and is therefore Wa-7 in age as well.

X-ray powder diffraction data show that the highest temperature solid phase of C4F8 has an orientationally disordered body-centered cubic structure, a = 7.06(3)Å, with two molecules per cell.

Borings in fossil turtle shells collected from the lowermost beds of the early Eocene Cathedral Bluffs Tongue of the Wasatch Formation in the northwestern part of the Green River Basin near South Pass, Wyoming, are herein described. Individual turtle shells in the study area are characterized by as few as one or two and as many as >100 borings. The borings include both non-penetrative forms (those which do not pass fully though the shell) as well as penetrative forms (those which pass fully from the exterior to the interior surface of the shell). All non-penetrative forms occur on external surfaces of the carapace and plastron (i.e. those that would have been accessible while the host taxon was alive). Two new ichnogenera and four new ichnospecies are established to describe these borings. Karethraichnus (new ichnogenus) includes three ichnospecies: K. lakkos (new ichnospecies), K. kulindros (new ichnospecies), and K. fiale (new ichnospecies). Karethraichnus lakkos are shallow (non-penetrating), hemispherical pits with rounded, to flattened bases. Karethraichnus kulindros are deep, non-penetrative traces with a cylindrical profile, an axis approximately perpendicular to the substrate surface and with rounded to flattened, hemispherical termini. Karethraichnus fiale are penetrative traces with a cylindrical to bi-convex or flask-shaped profile, and an axis approximately perpendicular to the substrate surface. Thatchtelithichnus (new ichnogenus) Thatchtelithichnus holmani (new ichnospecies) consist of non-penetrative borings into a bone substrate. They consist of a ring-shaped trace, with a central pedestal or platform. The position of the borings on the shells, and evidence of syn-emplacement healing of the borings in several of the turtles, indicates that these borings were emplacement by ectoparasites/mesoparasites while the animals were living. Similar traces in modern emydid turtles are attributed to ticks, leeches, or spirorchid liver flukes.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.