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The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
The Brechin Lagerstätte of southern Ontario contains an exceptionally diverse and well-preserved Late Ordovician (Katian) crinoid fauna. We describe four genera and eight species of camerate crinoids from the Brechin Lagerstätte, including six new species. Consequently, the total diversity of the fauna now stands at 27 genera and 39 nominal species, thereby making it the most taxonomically diverse Ordovician crinoid fauna known. Taxa described include the diplobathrid Pararchaeocrinus kiddi new species and the monobathrids Glyptocrinus ramulosus Billings, 1856, Periglyptocrinus priscus (Billings, 1857a), Periglyptocrinus astricus new species, Periglyptocrinus kevinbretti new species, Periglyptocrinus mcdonaldi new species, Periglyptocrinus silvosus new species, and Abludoglyptocrinus steinheimerae new species. We summarize the taxonomic composition, diversity, and abundance distribution of all known crinoids from the Brechin Lagerstätte to better characterize the paleoecological structure and complexity of the community. We establish that the fauna is dominated by the subclass Pentacrinoidea, both in terms of abundance and species richness. In addition, we analyze species-level abundance data using Relative Abundance Distribution (RAD) models to evaluate the ecological complexity of the paleocommunity. We found that community structure of the Brechin Lagerstätte is best explained by an ecologically ‘complex’ RAD model, which suggests that species partitioned niches along multiple resource axes and/or the presence of multiple ecological ways of life. These results indicate that the Brechin Lagerstätte is significant not only for being the most taxonomically diverse Katian crinoid assemblage, but also for being an early ecologically complex fauna that developed in the wake of the Great Ordovician Biodiversification Event.
OBJECTIVES/GOALS: To quantify clinical exam in total knee arthroplasty by answering the following questions: (1) What are the magnitudes of forces applied by surgeons during the varus-valgus exam? (2) Is the choice of tibial insert thickness related to the magnitude of the applied forces? (3) How accurately does a surgeon estimate the gaps in the varus-valgus exam? METHODS/STUDY POPULATION: Three cadaveric knees were implanted with standard TKA trial implants. Four pliable force sensors were wrapped around the foot and ankle of each cadaver to measure the push-pull forces applied during the varus-valgus exam. Six surgeons with varying experience independently conducted a varus-valgus exam in extension and flexion and reported the gaps that they observed. Motion capture was used to measure the gaps between femur and tibia by placing cluster of reflective markers on femur and tibia. Subsequently, each surgeon chose the tibial insert that they thought best fit each knee. The measured peak applied forces were related to the insert thickness and the measured gaps were compared to the observed gaps by surgeons. Since insert thickness was in 1 mm increments, 1 mm gap error was considered a meaningful difference. RESULTS/ANTICIPATED RESULTS: The peak forces varied among surgeons for each cadaver. In cadaver one, the peak forces in varus and valgus in extension were 48±20 and 20±12 N, and in flexion were 27±14 and 8±11 N. Peak forces in cadavers two and three were similar; in varus and valgus in extension, 24±14 and 35±10 N, and in flexion, 23±12 and 20±10 N, respectively. It was observed that the larger the valgus force in extension, the thinner was the inserts choice (β = −0.08 mm/N, p = 0.012). In extension, the difference between estimated gaps and measured gaps was > 1 mm for 36% of all assessments and 91% of gaps were underestimated. Only one measure, however, was underestimated by > 2 mm. In flexion, gap estimates were > 1 mm for 35% of all measurements and 59% of all measurements were overestimated. Four measures were overestimated, and one was underestimated by > 2 mm. DISCUSSION/SIGNIFICANCE OF IMPACT: We found that the applied forces varied among surgeons and a negative association between insert thickness and forces in extension valgus exam. We also found that error in gap estimates among surgeons was > 1 mm a third of the time and that underestimation is more common in full extension, which may lead to using smaller inserts that affect knee stability. CONFLICT OF INTEREST DESCRIPTION: The corresponding author has no COI but my coauthors had the following COI:
1. Royalties from a company or supplier: Zimmer; Stryker; Exactech, Inc; Lima; Mathys Ltd.
2. Speakers bureau/paid presentations for a company or supplier Acelity; Flexion Therapeutics; Smith & Nephew; Exactech, Inc; Mallinckrodt Pharmaceuticals; Stryker.
3B. Paid consultant for a company or supplier Acelity; DePuy Synthes; Exactech, Inc; Flexion Therapeutics; Intellijoint; Smith & Nephew; Zimmer; Stryker
4. Stock or stock options in a company or supplier Imagen; Insight Medical; Intellijoint; Parvizi Surgical Innovation; OrthAlign; Orthobond.
5. Research support from a company or supplier as a Principal Investigator Acelity; Exactech, Inc; Intellijoint; Smith & Nephew; Mallinckrodt Pharmaceuticals; Stryker; Lima.
6. Royalties, financial or material support from publishers (The following conflicts were disclosed) Exactech, Inc.
7. Medical/Orthopaedic publications editorial/governing board Bone and Joint Journal 360; Journal of Orthopaedics and Traumatology; Techniques in Orthopaedics.
8. Board member/committee appointments for a society Knee Society; Eastern Orthopedic Association.
Upper Ordovician (Katian) strata of the Lake Simcoe region of Ontario record a spectacularly diverse and abundant echinoderm fauna known as the Brechin Lagerstätte. Despite recognition as the most taxonomically diverse Katian crinoid paleocommunity, the Brechin Lagerstätte has received relatively little taxonomic study since Frank Springer published his classic monograph on the “Kirkfield fauna” in 1911.
Using a new collection of exceptionally preserved material, we evaluate all dicyclic inadunate crinoids occurring in the Brechin Lagerstätte, which is predominantly comprised of cladids (Eucladida and Flexibilia). We document 15 species across 11 genera, including descriptions of two new genera and four new species. New taxa include Konieckicrinus brechinensis n. gen. n. sp., K. josephi n. gen. n. sp., Simcoecrinus mahalaki n. gen. n. sp., and Dendrocrinus simcoensis n. sp.
Although cladids are not commonly considered major components of the Early Paleozoic Crinoid Macroevolutionary Fauna, which is traditionally conceived as dominated by disparids and diplobathrid camerates, they are the most diverse major lineage of crinoids occurring in the Brechin Lagerstätte. This unexpected result highlights the important roles of specimen-based taxonomy and systematic revisions in the study of large-scale diversity patterns.
A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
Keith Falkner’s invigorating significance for the RCM in the 1960s was no less than Hugh Allen’s had been in the interwar period. Falkner came to the College after a formative time at Cornell University in the United States, whose distinguished music faculty had introduced him to American musicology and early and contemporary musical repertoires. Falkner’s very individual ‘can do’ mindset encouraged him to challenge the RCM Council to raise the money the College needed, while his wide range of personal and musical sympathies made him very approachable to the RCM students. Falkner appreciated the potential of the RCM’s historic collections, while also being aware of the significant benefit of such technological developments as an electronic music studio. Under Falkner, the RCM’s library service was rationalized, and students were encouraged to perform outside the College. Falkner linked the RCM into the Association of European Conservatoires. He increased the range of subjects students could study, to include the guitar and Baroque instruments and the number of brass and woodwind students increased. Falkner took a robust attitude to improving professors’ pay.
The First War concluded the RCM’s Victorian and Edwardian history. As Chapter 6 recounts, when the College began to function again under Hugh Allen’s leadership, it would be adapting itself to a very different cultural and social age. It would also be in mourning, for Parry himself, and also for its students who had been killed and maimed, physically and mentally, by their experiences. We have a good sense of what Parry felt by the Director’s address he gave in September 1914. His first concern was for RCM students exposed to danger. As he expressed it: ‘[they] are gifted in a rare and special way. Some of them are so gifted that their loss could hardly be made good.