Convergent evolution of quadrupedality in ornithischian dinosaurs was achieved through disparate forelimb muscle mechanics.

The secondary evolution of quadrupedality from bipedal ancestry is a rare evolutionary transition in tetrapods yet occurred convergently at least three times within ornithischian dinosaurs. Despite convergently evolving quadrupedal gait, ornithischians exhibited variable anatomy, particularly in the forelimbs, which underwent a major functional change from assisting in foraging and feeding in bipeds to becoming principal weight-bearing components of the locomotor system in quadrupeds. Here, we use three-dimensional multi-body dynamics models to demonstrate quantitatively that different quadrupedal ornithischian clades evolved distinct forelimb musculature, particularly around the shoulder. We find that major differences in glenohumeral abduction-adduction and long axis rotation muscle leverages were key drivers of mechanical disparity, thereby refuting previous hypotheses about functional convergence in major clades. Elbow muscle leverages were also disparate across the major ornithischian lineages, although high elbow extension muscle leverages were convergent between most quadrupeds. Unlike in ornithischian hind limbs, where differences are more closely tied to functional similarity than phylogenetic relatedness, mechanical disparity in ornithischian forelimbs appears to have been shaped primarily by phylogenetic constraints. Differences in ancestral bipedal taxa within each clade may have resulted in disparate ecomorphological constraints on the evolutionary pathways driving divergence in their quadrupedal descendants.

Back to the bones: do muscle area assessment techniques predict functional evolution across a macroevolutionary radiation?

Measures of attachment or accommodation area on the skeleton are a popular means of rapidly generating estimates of muscle proportions and functional performance for use in large-scale macroevolutionary studies. Herein, we provide the first evaluation of the accuracy of these muscle area assessment (MAA) techniques for estimating muscle proportions, force outputs and bone loading in a comparative macroevolutionary context using the rodent masticatory system as a case study. We find that MAA approaches perform poorly, yielding large absolute errors in muscle properties, bite force and particularly bone stress. Perhaps more fundamentally, these methods regularly fail to correctly capture many qualitative differences between rodent morphotypes, particularly in stress patterns in finite-element models. Our findings cast doubts on the validity of these approaches as means to provide input data for biomechanical models applied to understand functional transitions in the fossil record, and perhaps even in taxon-rich statistical models that examine broad-scale macroevolutionary patterns. We suggest that future work should go back to the bones to test if correlations between attachment area and muscle size within homologous muscles across a large number of species yield strong predictive relationships that could be used to deliver more accurate predictions for macroevolutionary and functional studies.

Increase your Confidence in Opioid Prescribing: Marketing Messages in Continuing Medical Education Activities on ER/LA Opioids.

BACKGROUND: Overprescription of opioids has fueled an epidemic of addiction and overdose deaths. The FDA required manufacturers of extended-release/long-acting (ER/LA) opioids to fund continuing medical education (CME) on opioids as part of a Risk Evaluation and Mitigation Strategy (REMS). OBJECTIVES: We sought to determine whether industry-funded REMS on long-acting opioids were consistent with the FDA's goal to reduce serious, adverse outcomes resulting from inappropriate prescribing, misuse, and abuse. STUDY DESIGN: In 2018, we analyzed all internet-based REMS CME activities funded by the REMS Program Companies (RPC), a consortium of ER/LA opioid manufacturers. METHODS: We utilized systematic narrative thematic analysis, an inductive approach that allows for mapping of concepts and meanings across a body of data by identifying, recording, analyzing, and refining key narrative points, called "themes". Authors viewed all REMS activities multiple times. RESULTS: Ten themes were identified, all of which were at least somewhat incongruent with federal guidelines and their goals: 1. Chronic pain is a common, under-treated problem. 2.Chronic pain is a chronic disease.3.Opioids are an appropriate treatment for chronic pain. 4.LAs are more appropriate than immediate-release (IR) opioids for chronic pain. 5.Tolerance is normal, expected, and beneficial. 6. Opioid rotation" can maximize analgesia and minimize adverse effects.7. There is no population for whom opioids are absolutely contraindicated or inappropriate. 8. Screening and monitoring tools are effective for preventing opioid-related problems. 9. Opioid related adverse effects, such as respiratory depression and addiction, are due only to misuse and abuse. Addiction, overdose, and death are due to street drugs such as heroin and fentanyl, not prescription opioids.Themes and statements repeated in these activities were inconsistent with current medical knowledge, evidence-based federal guidelines, and FDA goals. LIMITATIONS: We evaluated only online, not live, CME. We also did not evaluate individual conflicts of interest of faculty. CONCLUSIONS: Industry-funded REMS-compliant CME on opioids contain messages that misrepresent scientific evidence and may foster overprescribing of opioids.

Evolutionary biomechanics: hard tissues and soft evidence?

Biomechanical modelling is a powerful tool for quantifying the evolution of functional performance in extinct animals to understand key anatomical innovations and selective pressures driving major evolutionary radiations. However, the fossil record is composed predominantly of hard parts, forcing palaeontologists to reconstruct soft tissue properties in such models. Rarely are these reconstruction approaches validated on extant animals, despite soft tissue properties being highly determinant of functional performance. The extent to which soft tissue reconstructions and biomechanical models accurately predict quantitative or even qualitative patterns in macroevolutionary studies is therefore unknown. Here, we modelled the masticatory system in extant rodents to objectively test the ability of current muscle reconstruction methods to correctly identify quantitative and qualitative differences between macroevolutionary morphotypes. Baseline models generated using measured soft tissue properties yielded differences in muscle proportions, bite force, and bone stress expected between extant sciuromorph, myomorph, and hystricomorph rodents. However, predictions from models generated using reconstruction methods typically used in fossil studies varied widely from high levels of quantitative accuracy to a failure to correctly capture even relative differences between macroevolutionary morphotypes. Our novel experiment emphasizes that correctly reconstructing even qualitative differences between taxa in a macroevolutionary radiation is challenging using current methods. Future studies of fossil taxa should incorporate systematic assessments of reconstruction error into their hypothesis testing and, moreover, seek to expand primary datasets on muscle properties in extant taxa to better inform soft tissue reconstructions in macroevolutionary studies.

Description and etiology of paleopathological lesions in the type specimen of Parasaurolophus walkeri (Dinosauria: Hadrosauridae), with proposed reconstructions of the nuchal ligament.

Paleopathology, or the study of ancient injuries and diseases, can enable the ecology and life history of extinct taxa to be deciphered. Large-bodied ornithopods are the dinosaurs with the highest frequencies of paleopathology reported to-date. Among these, the crested hadrosaurid Parasaurolophus walkeri is one of the most famous, largely due to its dramatic elongated and tubular nasal crest. The holotype of Parasaurolophus walkeri at the Royal Ontario Museum, Canada, displays several paleopathologies that have not been discussed in detail previously: a dental lesion in the left maxilla, perhaps related to periodontal disease; callus formation associated with fractures in three dorsal ribs; a discoidal overgrowth above dorsal neural spines six and seven; a cranially oriented spine in dorsal seven, that merges distally with spine six; a V-shaped gap between dorsal spines seven and eight; and a ventral projection of the pubic process of the ilium which covers, and is fused with, the lateral side of the iliac process of the pubis. These lesions suggest that the animal suffered from one or more traumatic events, with the main one causing a suite of injuries to the anterior aspect of the thorax. The presence of several lesions in a single individual is a rare observation and, in comparison with a substantial database of hadrosaur paleopathological lesions, has the potential to reveal new information about the biology and behavior of these ornithopods. The precise etiology of the iliac abnormality is still unclear, although it is thought to have been an indirect consequence of the anterior trauma. The discoidal overgrowth above the two neural spines also seems to be secondary to the severe trauma inflicted on the ribs and dorsal spines, and probably represents post-traumatic ossification of the base of the nuchal ligament. The existence of this structure has previously been considered in hadrosaurs and dinosaurs more generally through comparison of origin and insertion sites in modern diapsids (Rhea americana, Alligator mississippiensis, Iguana iguana), but its presence, structure, and origin-attachment sites are still debated. The V-shaped gap is hypothesized as representing the point between the stresses of the nuchal ligament, pulling the anterior neural spines forward, and the ossified tendons pulling the posterior neural spines backward. Different reconstructions of the morphology of the structure based on the pathological conditions affecting the neural spines of ROM 768 are proposed. Finally, we review the history of reconstructions for Parasaurolophus walkeri showing how erroneous misconceptions have been perpetuated over time or have led to the development of new hypotheses, including the wide neck model supported in the current research.