Calvarial suture interdigitation in hadrosaurids (Ornithischia: Ornithopoda): Perspectives through ontogeny and evolution.

Lambeosaurine hadrosaurids exhibited extreme modifications to the skull, where the premaxillae, nasals, and prefrontals were modified to form their iconic supracranial crests. This morphology contrasts with their sister group, Hadrosaurinae, which possessed the plesiomorphic arrangement of bones. Although studies have discussed differences between lambeosaurine and hadrosaurine skull morphology and ontogeny, there is little information detailing suture modifications through ontogeny and evolution. Suture morphology is of particular interest due to its correlation with the mechanical loading of the skull in extant vertebrates. We quantify and contrast the morphology of calvarial sutures in iguanodontians and ontogenetic series of Corythosaurus and Gryposaurus to test whether the evolution of lambeosaurine crests impacted the mechanical loading of the skull. We found that suture interdigitation (SI) increases through ontogeny in hadrosaurids, although this increase is more extreme in Corythosaurus than Gryposaurus, and overall suture complexity (i.e., overall shape) remained constant. Lambeosaurines also have higher SI than other iguanodontians, even in crestless juveniles, suggesting that increased sinuosity is unrelated to the structural support of the crest. Hadrosaurines and basal iguanodontians did not differ. Similarly, lambeosaurines have more complexly shaped sutures than hadrosaurines and basal iguanodontians, while the latter two groups do not differ. Taken together, these results suggest that lambeosaurine calvarial sutures are more interdigitated than other iguanodontians, and although suture sinuosity increased through ontogeny, the suture shape remained constant. These ontogenetic and evolutionary patterns suggest that increased suture complexity in lambeosaurines coincided with crest evolution, and corresponding modifications to their facial skeleton altered the distribution of stress while feeding.

Reconstructing locomotor ecology of extinct avialans: a case study of Ichthyornis comparing sternum morphology and skeletal proportions.

Avian skeletal morphology is associated with locomotor function, including flight style, swimming and terrestrial locomotion, and permits informed inferences on locomotion in extinct taxa. The fossil taxon Ichthyornis (Avialae: Ornithurae) has long been regarded as highly aerial, with flight similar to terns or gulls (Laridae), and skeletal features resembling foot-propelled diving adaptations. However, rigorous testing of locomotor hypotheses has yet to be performed on Ichthyornis, despite its notable phylogenetic position as one of the most crownward stem birds. We analysed separate datasets of three-dimensional sternal shape (geometric morphometrics) and skeletal proportions (linear measurements across the skeleton), to examine how well these data types predict locomotor traits in Neornithes. We then used this information to infer locomotor capabilities of Ichthyornis. We find strong support for both soaring and foot-propelled swimming capabilities in Ichthyornis. Further, sternal shape and skeletal proportions provide complementary information on avian locomotion: skeletal proportions allow better predictions of the capacity for flight, whereas sternal shape predicts variation in more specific locomotor abilities such as soaring, foot-propelled swimming and escape burst flight. These results have important implications for future studies of extinct avialan ecology and underscore the importance of closely considering sternum morphology in investigations of fossil bird locomotion.

Osteohistological and taphonomic life-history assessment of Edmontosaurus annectens (Ornithischia: Hadrosauridae) from the Late Cretaceous (Maastrichtian) Ruth Mason dinosaur quarry, South Dakota, United States, with implication for ontogenetic segregation between juvenile and adult hadrosaurids.

The Late Cretaceous (Maastrichtian) Ruth Mason Dinosaur Quarry (RMDQ) represents a monodominant Edmontosaurus annectens bonebed from the Hell Creek Formation of South Dakota and has been determined as a catastrophic death assemblage likely belonging to a single population, providing an ideal sample to investigate hadrosaurid growth and population dynamics. For this study, size-frequency distributions were constructed from linear measurements of long bones (humeri, femora, tibiae) from RMDQ that revealed five relatively distinct size classes along a generally right-skewed distribution, which is consistent with a catastrophic assemblage. To test the relationship between morphological size ranges and ontogenetic age classes, subsets from each size-frequency peak were transversely thin-sectioned at mid-diaphysis to conduct an ontogenetic age assessment based on growth marks and observations of the bone microstructure. When combining these independent datasets, growth marks aligned with size-frequency peaks, with the exclusion of the overlapping subadult-adult size range, indicating a strong size-age relationship in early ontogeny. A growth curve analysis of tibiae indicated that E. annectens exhibited a similar growth trajectory to the Campanian hadrosaurid Maiasaura, although attaining a much larger asymptotic body size by about 9 years of age, further suggesting that the clade as a whole may have inherited a similar growth strategy. This rich new dataset for E. annectens provides new perspectives on other hypotheses of hadrosaurid life history. When the RMDQ population was compared with size distributions from other hadrosaurid bonebed assemblages, juveniles (categorized as ages one and two) were either completely absent from or heavily underrepresented in the samples, providing support for the hypothesized segregation between juvenile and adult hadrosaurids. Osteohistological comparison with material from polar and temperate populations of Edmontosaurus revealed that previous conclusions correlating osteohistological growth patterns with the strength of environmental stressors were a result of sampling non-overlapping ontogenetic growth stages.

Neurosensory anatomy of Varanopidae and its implications for early synapsid evolution.

Varanopids are a group of Palaeozoic terrestrial amniotes which represent one of the earliest-diverging groups of synapsids, but their palaeoneurology has gone largely unstudied and recent analyses have challenged their traditional placement within synapsids. We utilized computed tomography (CT) to study the virtual cranial and otic endocasts of six varanopids, including representative taxa of both mycterosaurines and varanodontines. Our results show that the varanopid brain is largely plesiomorphic, being tubular in shape and showing no expansion of the cerebrum or olfactory bulbs, but is distinct in showing highly expanded floccular fossae. The housing of the varanopid bony labyrinth is also distinct, in that the labyrinth is bounded almost entirely by the supraoccipital-opisthotic complex, with the prootic only bordering the ventral portion of the vestibule. The bony labyrinth is surprisingly well-ossified, clearly preserving the elliptical, sub-orthogonal canals, prominent ampullae, and the short, undifferentiated vestibule; this high degree of ossification is similar to that seen in therapsid synapsids and supports the traditional placement of varanopids within Synapsida. The enlarged anterior canal, together with the elliptical, orthogonal canals and enlarged floccular fossa, lend support for the fast head movements indicated by the inferred predatory feeding mode of varanopids. Reconstructed neurosensory anatomy indicates that varanopids may have a much lower-frequency hearing range compared to more derived synapsids, suggesting that, despite gaining some active predatory features, varanopids retain plesiomorphic hearing capabilities. As a whole, our data reveal that the neuroanatomy of pelycosaur-grade synapsids is far more complex than previously anticipated.

Palaeopathological evidence for intraspecific combat in ankylosaurid dinosaurs.

Ankylosaurid dinosaurs were heavily armoured herbivores with tails modified into club-like weapons. These tail clubs have widely been considered defensive adaptations wielded against predatory theropod dinosaurs. Here we argue instead that ankylosaurid tail clubs were sexually selected structures used primarily for intraspecific combat. We found pathological osteoderms (armour plates) in the holotype specimen of Zuul crurivastator, which are localized to the flanks in the hip region rather than distributed randomly across the body, consistent with injuries inflicted by lateral tail-swinging and ritualized combat. We failed to find convincing evidence for predation as a key selective pressure in the evolution of the tail club. High variation in tail club size through time, and delayed ontogenetic growth of the tail club further support the sexual selection hypothesis. There is little doubt that the tail club could have been used in defence when needed, but our results suggest that sexual selection drove the evolution of this impressive weapon. This changes the prevailing view of ankylosaurs, suggesting they were behaviorally complex animals that likely engaged in ritualized combat for social dominance as in other ornithischian dinosaurs and mammals.

The relationship between sternum variation and mode of locomotion in birds.

BACKGROUND: The origin of powered avian flight was a locomotor innovation that expanded the ecological potential of maniraptoran dinosaurs, leading to remarkable variation in modern birds (Neornithes). The avian sternum is the anchor for the major flight muscles and, despite varying widely in morphology, has not been extensively studied from evolutionary or functional perspectives. We quantify sternal variation across a broad phylogenetic scope of birds using 3D geometric morphometrics methods. Using this comprehensive dataset, we apply phylogenetically informed regression approaches to test hypotheses of sternum size allometry and the correlation of sternal shape with both size and locomotory capabilities, including flightlessness and the highly varying flight and swimming styles of Neornithes. RESULTS: We find evidence for isometry of sternal size relative to body mass and document significant allometry of sternal shape alongside important correlations with locomotory capability, reflecting the effects of both body shape and musculoskeletal variation. Among these, we show that a large sternum with a deep or cranially projected sternal keel is necessary for powered flight in modern birds, that deeper sternal keels are correlated with slower but stronger flight, robust caudal sternal borders are associated with faster flapping styles, and that narrower sterna are associated with running abilities. Correlations between shape and locomotion are significant but show weak explanatory power, indicating that although sternal shape is broadly associated with locomotory ecology, other unexplored factors are also important. CONCLUSIONS: These results display the ecological importance of the avian sternum for flight and locomotion by providing a novel understanding of sternum form and function in Neornithes. Our study lays the groundwork for estimating the locomotory abilities of paravian dinosaurs, the ancestors to Neornithes, by highlighting the importance of this critical element for avian flight, and will be useful for future work on the origin of flight along the dinosaur-bird lineage.

Optimizing Spinal Anesthesia in Same-Day Discharge Knee Arthroplasty Patients: Mepivacaine Versus Ropivacaine.

BACKGROUND: Short-acting spinal anesthetics are playing an increasing role in same-day discharge total joint arthroplasty though their direct comparison remains to be studied. Therefore, this study aims to compare two formulations of spinal anesthesia regarding time to discharge following knee arthroplasty surgery. METHODS: A retrospective study was performed on 207 patients who underwent unicompartmental knee arthroplasty (UKA, n = 172) and total knee arthroplasty (TKA, n = 35) from May 2018 to December 2020 at a single institution and were discharged the same day. Two formulations of the spinal anesthetic were routinely administered in this population: 1) mepivacaine 1.5% 3-4 mL (n = 184) and 2) ropivacaine 0.5% 2.3-2.7 mL (n = 23). Discharge times were subsequently compared between mepivacaine and ropivacaine spinal anesthesia for each surgical procedure and between surgical procedures. RESULTS: There was no significant difference in discharge times between patients receiving mepivacaine versus ropivacaine for UKA (202 minutes [range = 54-449] versus 218 minutes [range = 175-385], P = .45) or TKA (193 minutes [range = 68-384] versus 196 minutes [range = 68-412], P = .93). Similarly, no difference was found in discharge times between UKA and TKA patients receiving mepivacaine (P = .68) or ropivacaine (P = .51). CONCLUSION: There was no significant difference in discharge times between anesthetic agents among knee surgery patients. Therefore, either agent may be recommended for same-day discharge.

Management of blunt cerebrovascular injuries at a Canadian level 1 trauma centre: Are we meeting the grade?

BACKGROUND: Untreated blunt cerebrovascular injuries (BCVIs) are associated with high rates of death and disability due to stroke. We assessed alignment of clinical practice at our centre with current recommendations for management of BCVIs and examined rates of new and recurrent in-hospital stroke. METHODS: We retrospectively reviewed the BC Trauma Registry to identify all adult (age > 18 yr) patients with trauma with BCVIs at the largest level 1 trauma centre in British Columbia, Canada, from Apr. 1, 2013, to Mar. 31, 2018. We evaluated the registry, hospital databases and patient charts to assess alignment with guidelines for early initiation of appropriate antithrombotic therapy and follow-up imaging, and to ascertain short-term outcomes. RESULTS: A total of 186 patients met the inclusion criteria. Just over half of BCVIs (97 [52.2%]) were Biffl grade 1-2. The majority of patients were treated with acetylsalicylic acid monotherapy (144/162 [88.9%]) or low-molecular-weight heparin (2/162 [1.2%]). Although guidelines recommend repeat imaging at 7-10 days to reassess the injury and guide duration of therapy, only 61/171 patients (35.7%) underwent repeat imaging within 7 days. Neuroimaging within 3 months after injury showed brain infarction in 29 patients (15.6%). CONCLUSION: Antithrombotic therapy was initiated in the majority of eligible patients with BCVIs, but completion of follow-up imaging and documentation of clear outpatient care plans were suboptimal. This finding shows the need for routine multidisciplinary management to facilitate standardization of care for this complex population.

Growth variability, dimensional scaling, and the interpretation of osteohistological growth data.

Osteohistological data are commonly used to study the life history of extant and extinct tetrapods. While recent advances have permitted detailed reconstructions of growth patterns, physiology and other features using these data, they are most commonly used in assessments of ontogenetic stage and relative growth in extinct animals. These methods have seen widespread adoption in recent years, rapidly becoming a common component of the taxonomic description of new fossil taxa, but are often applied without close consideration of the sources of variation present or the dimensional scaling relationships that exist among different osteohistological measurements. Here, we use a combination of theoretical models and empirical data from a range of extant and extinct tetrapods to review sources of variability in common osteohistological measurements, their dimensional scaling relationships and the resulting interpretations that can be made from those data. In particular, we provide recommendations on the usage and interpretation of growth mark spacing/zonal thickness data, when these are likely to be unreliable, and under what conditions they can provide useful inferences for studies of growth and life history.

A Novel Immune Modulator for Patients With Necrotizing Soft Tissue Infections (NSTI): Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod (AB 103).

BACKGROUND AND OBJECTIVE: Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI. METHODS: Randomized, double-blind, placebo-controlled trial of single dose reltecimod (0.5 mg/kg) administered within 6 hours of NSTI diagnosis at 65 of 93 study sites. Inclusion: surgical confirmation of NSTI and organ dysfunction [modified Sequential Organ Failure Assessment Score (mSOFA) score ≥3]. Primary analysis was modified Intent-to-Treat (mITT), responder analysis using a previously validated composite endpoint, necrotizing infection clinical composite endpoint, defined as: alive at day 28, ≤3 debridements, no amputation beyond first operation, and day 14 mSOFA ≤1 with ≥3 point reduction (organ dysfunction resolution). A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding. RESULTS: Two hundred ninety patients were enrolled, mITT (Reltecimod 142, Placebo 148): mean age 55 ±â€Š15 years, 60% male, 42.4% diabetic, 28.6% perineal infection, screening mSOFA mean 5.5 ±â€Š2.4. Twenty-eight-day mortality was 15% in both groups. mITT necrotizing infection clinical composite endpoint success was 48.6% reltecimod versus 39.9% placebo, P = 0.135 and PP was 54.3% reltecimod versus 40.3% placebo, P = 0.021. Resolution of organ dysfunction was 65.1% reltecimod versus 52.6% placebo, P = 0.041, mITT and 70.9% versus 53.4%, P = 0.005, PP. CONCLUSION: Early administration of reltecimod in severe NSTI resulted in a significant improvement in the primary composite endpoint in the PP population but not in the mITT population. Reltecimod was associated with improved resolution of organ dysfunction and hospital discharge status.

Computed tomography analysis of the cranium of Champsosaurus lindoei and implications for the choristoderan neomorphic ossification.

Choristoderes are extinct neodiapsid reptiles that are well known for their unusual cranial anatomy, possessing an elongated snout and expanded temporal arches. Although choristodere skulls are well described externally, their internal anatomy remains unknown. An internal description was needed to shed light on peculiarities of the choristodere skull, such as paired gaps on the ventral surface of the skull that may pertain to the fenestra ovalis, and a putative neomorphic ossification in the lateral wall of the braincase. Our goals were: (i) to describe the cranial elements of Champsosaurus lindoei in three dimensions; (ii) to describe paired gaps on the ventral surface of the skull to determine if these are indeed the fenestrae ovales; (iii) to illustrate the morphology of the putative neomorphic bone; and (iv) to consider the possible developmental and functional origins of the neomorph. We examined the cranial anatomy of the choristodere Champsosaurus lindoei (CMN 8920) using high-resolution micro-computed tomography scanning. We found that the paired gaps on the ventral surface of the skull do pertain to the fenestrae ovales, an unusual arrangement that may be convergent with some plesiosaurs, some aistopods, and some urodeles. The implications of this morphology in Champsosaurus are unknown and will be the subject of future work. We found that the neomorphic bone is a distinct ossification, but is not part of the wall of the brain cavity or the auditory capsule. Variation in the developmental pathways of cranial bones in living amniotes was surveyed to determine how the neomorphic bone may have developed. We found that the chondrocranium and splanchnocranium show little to no variation across amniotes, and the neomorphic bone is therefore most likely to have developed from the dermatocranium; however, the stapes is a pre-existing cranial element that is undescribed in choristoderes and may be homologous with the neomorphic bone. If the neomorphic bone is not homologous with the stapes, the neomorph likely developed from the dermatocranium through incomplete fusion of ossification centres from a pre-existing bone, most likely the parietal. Based on the apparent morphology of the neomorph in Coeruleodraco, the neomorph was probably too small to play a significant structural role in the skull of early choristoderes and it may have arisen through non-adaptive means. In neochoristoderes, such as Champsosaurus, the neomorph was likely recruited to support the expanded temporal arches.

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.

Intrapleural Tissue Plasminogen Activator for Traumatic Retained Hemothorax.

Objective: To describe the efficacy, safety, dosing regimen, and administration technique of intrapleural alteplase for the treatment of retained hemothorax. Data Sources: A PubMed, EMBASE, and Google Scholar search (January 2000 to February 2019) was conducted with the search terms intrapleural, fibrinolytic, fibrinolysis, alteplase, tissue plasminogen activator, and hemothorax. Study Selection and Data Extraction: Articles were included if they described the use of intrapleural alteplase in adult patients with a retained hemothorax; single patient case reports and abstracts were excluded. Data Synthesis: A total of 6 retrospective reviews and 1 meta-analysis were identified for inclusion. A variety of dosing strategies have been defined for the administration of intrapleural alteplase ranging from 6 to 100 mg, volume of fluid from 50 to 120 mL of normal saline, and the number of total doses has ranged from 1 to 8 over the treatment course. A majority of studies showed a greater than 80% success rate and less than 7% bleeding rate. Relevance to Patient Care and Clinical Practice: Because of the paucity of data for use of alteplase in retained hemothorax and administration of a high-risk medication, this review provides dosing and administration recommendations based on reported safety and efficacy. Conclusion: Administration of intrapleural alteplase should be considered in patients with retained hemothorax as an alternative to surgical intervention. In contrast to intrapleural alteplase administration for other indications such as empyema, higher doses and volumes of alteplase are recommended for retained hemothorax.

A Systematic Review of the Risks and Benefits of Venous Thromboembolism Prophylaxis in Traumatic Brain Injury.

BACKGROUND: Patients suffering from traumatic brain injury (TBI) are at increased risk of venous thromboembolism (VTE). However, initiation of pharmacological venous thromboprophylaxis (VTEp) may cause further intracranial hemorrhage. We reviewed the literature to determine the postinjury time interval at which VTEp can be administered without risk of TBI evolution and hematoma expansion. METHODS: MEDLINE and EMBASE databases were searched. Inclusion criteria were studies investigating timing and safety of VTEp in TBI patients not previously on oral anticoagulation. Two investigators extracted data and graded the papers' levels of evidence. Randomized controlled trials were assessed for bias according to the Cochrane Collaboration Tool and Cohort studies were evaluated for bias using the Newcastle-Ottawa Scale. We performed univariate meta-regression analysis in an attempt to identify a relationship between VTEp timing and hemorrhagic progression and assess study heterogeneity using an I 2 statistic. RESULTS: Twenty-one studies were included in the systematic review. Eighteen total studies demonstrated that VTEp postinjury in patients with stable head computed tomography scan does not lead to TBI progression. Fourteen studies demonstrated that VTEp administration 24 to 72 hours postinjury is safe in patients with stable injury. Four studies suggested that administering VTEp within 24 hours of injury in patients with stable TBI does not lead to progressive intracranial hemorrhage. Overall, meta-regression analysis demonstrated that there was no relationship between rate of hemorrhagic progression and VTEp timing. CONCLUSIONS: Literature suggests that administering VTEp 24 to 48 hours postinjury may be safe for patients with low-hemorrhagic-risk TBIs and stable injury on repeat imaging.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway.

Perioperative malnutrition has proven to be challenging to define, diagnose, and treat. Despite these challenges, it is well known that suboptimal nutritional status is a strong independent predictor of poor postoperative outcomes. Although perioperative caregivers consistently express recognition of the importance of nutrition screening and optimization in the perioperative period, implementation of evidence-based perioperative nutrition guidelines and pathways in the United States has been quite limited and needs to be addressed in surgery-focused recommendations. The second Perioperative Quality Initiative brought together a group of international experts with the objective of providing consensus recommendations on this important topic with the goal of (1) developing guidelines for screening of nutritional status to identify patients at risk for adverse outcomes due to malnutrition; (2) address optimal methods of providing nutritional support and optimizing nutrition status preoperatively; and (3) identifying when and how to optimize nutrition delivery in the postoperative period. Discussion led to strong recommendations for implementation of routine preoperative nutrition screening to identify patients in need of preoperative nutrition optimization. Postoperatively, nutrition delivery should be restarted immediately after surgery. The key role of oral nutrition supplements, enteral nutrition, and parenteral nutrition (implemented in that order) in most perioperative patients was advocated for with protein delivery being more important than total calorie delivery. Finally, the role of often-inadequate nutrition intake in the posthospital setting was discussed, and the role of postdischarge oral nutrition supplements was emphasized.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Patient-Reported Outcomes in an Enhanced Recovery Pathway.

Patient-reported outcomes (PROs) are measures of health status that come directly from the patient. PROs are an underutilized tool in the perioperative setting. Enhanced recovery pathways (ERPs) have primarily focused on traditional measures of health care quality such as complications and hospital length of stay. These measures do not capture postdischarge outcomes that are meaningful to patients such as function or freedom from disability. PROs can be used to facilitate shared decisions between patients and providers before surgery and establish benchmark recovery goals after surgery. PROs can also be utilized in quality improvement initiatives and clinical research studies. An expert panel, the Perioperative Quality Initiative (POQI) workgroup, conducted an extensive literature review to determine best practices for the incorporation of PROs in an ERP. This international group of experienced clinicians from North America and Europe met at Stony Brook, NY, on December 2-3, 2016, to review the evidence supporting the use of PROs in the context of surgical recovery. A modified Delphi method was used to capture the collective expertise of a diverse group to answer clinical questions. During 3 plenary sessions, the POQI PRO subgroup presented clinical questions based on a literature review, presented evidenced-based answers to those questions, and developed recommendations which represented a consensus opinion regarding the use of PROs in the context of an ERP. The POQI workgroup identified key criteria to evaluate patient-reported outcome measures (PROMs) for their incorporation in an ERP. The POQI workgroup agreed on the following recommendations: (1) PROMs in the perioperative setting should be collected in the framework of physical, mental, and social domains. (2) These data should be collected preoperatively at baseline, during the immediate postoperative time period, and after hospital discharge. (3) In the immediate postoperative setting, we recommend using the Quality of Recovery-15 score. After discharge at 30 and 90 days, we recommend the use of the World Health Organization Disability Assessment Scale 2.0, or a tailored use of the Patient-Reported Outcomes Measurement Information System. (4) Future study that consistently applies PROMs in an ERP will define the role these measures will have evaluating quality and guiding clinical care. Consensus guidelines regarding the incorporation of PRO measures in an ERP were created by the POQI workgroup. The inclusion of PROMs with traditional measures of health care quality after surgery provides an opportunity to improve clinical care.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Gastrointestinal Dysfunction Within an Enhanced Recovery Pathway for Elective Colorectal Surgery.

The primary driver of length of stay after bowel surgery, particularly colorectal surgery, is the time to return of gastrointestinal (GI) function. Traditionally, delayed GI recovery was thought to be a routine and unavoidable consequence of surgery, but this has been shown to be false in the modern era owing to the proliferation of enhanced recovery protocols. However, impaired GI function is still common after colorectal surgery, and the current literature is ambiguous with regard to the definition of postoperative GI dysfunction (POGD), or what is typically referred to as ileus. This persistent ambiguity has impeded the ability to ascertain the true incidence of the condition and study it properly within a research setting. Furthermore, a rational and standardized approach to prevention and treatment of POGD is needed. The second Perioperative Quality Initiative brought together a group of international experts to review the published literature and provide consensus recommendations on this important topic with the goal to (1) develop a rational definition for POGD that can serve as a framework for clinical and research efforts; (2) critically review the evidence behind current prevention strategies and provide consensus recommendations; and (3) develop rational treatment strategies that take into account the wide spectrum of impaired GI function in the postoperative period.

Development and Validation of Quality Criteria for Providing Patient- and Family-centered Injury Care.

OBJECTIVE: The aim of this study was to develop and evaluate the content validity of quality criteria for providing patient- and family-centered injury care. BACKGROUND: Quality criteria have been developed for clinical injury care, but not patient- and family-centered injury care. METHODS: Using a modified Research AND Development Corporation (RAND)/University of California, Los Angeles (UCLA) Appropriateness Methodology, a panel of 16 patients, family members, injury and quality of care experts serially rated and revised criteria for patient- and family-centered injury care identified from patient and family focus groups. The criteria were then sent to 384 verified trauma centers in the United States, Canada, Australia, and New Zealand for evaluation. RESULTS: A total of 46 criteria were rated and revised by the panel over 4 rounds of review producing 14 criteria related to clinical care (n = 4; transitions of care, pain management, patient safety, provider competence), communication (n = 3; information for patients/families; communication of discharge plans to patients/families, communication between hospital and community providers), holistic care (n = 4; patient hygiene, kindness and respect, family access to patient, social and spiritual support) and end-of-life care (n = 3; decision making, end-of-life care, family follow-up). Medical directors, managers, or coordinators representing 254 trauma centers (66% response rate) rated 12 criteria to be important (95% of responses) for patient- and family-centered injury care. Fewer centers rated family access to the patient (80%) and family follow-up after patient death (65%) to be important criteria. CONCLUSIONS: Fourteen-candidate quality criteria for patient- and family-centered injury care were developed and shown to have content validity. These may be used to guide quality improvement practices.

Disrupted Murine Gut-to-Human Liver Signaling Alters Bile Acid Homeostasis in Humanized Mouse Liver Models.

The humanized liver mouse model is being exploited increasingly for human drug metabolism studies. However, its model stability, intercommunication between human hepatocytes and mouse nonparenchymal cells in liver and murine intestine, and changes in extrahepatic transporter and enzyme expressions have not been investigated. We examined these issues in FRGN [fumarylacetoacetate hydrolase (Fah-/-), recombination activating gene 2 (Rag2-/-), and interleukin 2 receptor subunit gamma (IL-2rg -/-) triple knockout] on nonobese diabetic (NOD) background] and chimeric mice: mFRGN and hFRGN (repopulated with mouse or human hepatocytes, respectively). hFRGN mice showed markedly higher levels of liver cholesterol, biliary bilirubin, and bile acids (liver, bile, and plasma; mainly human forms, but also murine bile acids) but lower transforming growth factor beta receptor 2 (TGFBR2) mRNA expression levels (10%) in human hepatocytes and other proliferative markers in mouse nonparenchymal cells (Tgf-ß1) and cholangiocytes [plasma membrane-bound, G protein-coupled receptor for bile acids (Tgr5)], suggestive of irregular regeneration processes in hFRGN livers. Changes in gene expression in murine intestine, kidney, and brain of hFRGN mice, in particular, induction of intestinal farnesoid X receptor (Fxr) genes: fibroblast growth factor 15 (Fgf15), mouse ileal bile acid binding protein (Ibabp), small heterodimer partner (Shp), and the organic solute transporter alpha (Ostα), were observed. Proteomics revealed persistence of remnant murine proteins (cyotchrome P450 7α-hydroxylase (Cyp7a1) and other enzymes and transporters) in hFRGN livers and suggest the likelihood of mouse activity. When compared with normal human liver tissue, hFRGN livers showed lower SHP mRNA and higher CYP7A1 (300%) protein expression, consequences of tß- and tα-muricholic acid-mediated inhibition of the FXR-SHP cascade and miscommunication between intestinal Fgf15 and human liver fibroblast growth factor receptor 4 (FGFR4), as confirmed by the unchanged hepatic pERK/total ERK ratio. Dysregulation of hepatocyte proliferation and bile acid homeostasis in hFRGN livers led to hepatotoxicity, gallbladder distension, liver deformity, and other extrahepatic changes, making questionable the use of the preparation for drug metabolism studies.

Rates of dinosaur body mass evolution indicate 170 million years of sustained ecological innovation on the avian stem lineage.

Large-scale adaptive radiations might explain the runaway success of a minority of extant vertebrate clades. This hypothesis predicts, among other things, rapid rates of morphological evolution during the early history of major groups, as lineages invade disparate ecological niches. However, few studies of adaptive radiation have included deep time data, so the links between extant diversity and major extinct radiations are unclear. The intensively studied Mesozoic dinosaur record provides a model system for such investigation, representing an ecologically diverse group that dominated terrestrial ecosystems for 170 million years. Furthermore, with 10,000 species, extant dinosaurs (birds) are the most speciose living tetrapod clade. We assembled composite trees of 614-622 Mesozoic dinosaurs/birds, and a comprehensive body mass dataset using the scaling relationship of limb bone robustness. Maximum-likelihood modelling and the node height test reveal rapid evolutionary rates and a predominance of rapid shifts among size classes in early (Triassic) dinosaurs. This indicates an early burst niche-filling pattern and contrasts with previous studies that favoured gradualistic rates. Subsequently, rates declined in most lineages, which rarely exploited new ecological niches. However, feathered maniraptoran dinosaurs (including Mesozoic birds) sustained rapid evolution from at least the Middle Jurassic, suggesting that these taxa evaded the effects of niche saturation. This indicates that a long evolutionary history of continuing ecological innovation paved the way for a second great radiation of dinosaurs, in birds. We therefore demonstrate links between the predominantly extinct deep time adaptive radiation of non-avian dinosaurs and the phenomenal diversification of birds, via continuing rapid rates of evolution along the phylogenetic stem lineage. This raises the possibility that the uneven distribution of biodiversity results not just from large-scale extrapolation of the process of adaptive radiation in a few extant clades, but also from the maintenance of evolvability on vast time scales across the history of life, in key lineages.