An exquisitely preserved in-ovo theropod dinosaur embryo sheds light on avian-like prehatching postures

Despite the discovery of many dinosaur eggs and nests over the past 100 years, articulated in-ovo embryos are remarkably rare. Here we report an exceptionally preserved, articulated oviraptorid embryo inside an elongatoolithid egg, from the Late Cretaceous Hekou Formation of southern China. The head lies ventral to the body, with the feet on either side, and the back curled along the blunt pole of the egg, in a posture previously unrecognized in a non-avian dinosaur, but reminiscent of a late-stage modern bird embryo. Comparison to other late-stage oviraptorid embryos suggests that prehatch oviraptorids developed avian-like postures late in incubation, which in modern birds are related to coordinated embryonic movements associated with tucking — a behavior controlled by the central nervous system, critical for hatching success. We propose that such pre-hatching behavior, previously considered unique to birds, may have originated among non-avian theropods, which can be further investigated with additional discoveries of embryo fossils

Eggshell geochemistry reveals ancestral metabolic thermal regulation in Dinosauria

Studying the origin of avian thermoregulation is complicated by a lack of reliable methods to measure body temperatures in extinct dinosaurs. Evidence from bone histology and stable isotope analysis often relies on uncertain assumptions about the relationship between growth rate and body temperature, or the isotopic composition (δ18O) of body water. By contrast, clumped isotope (Δ47) paleothermometry, which relies on the binding of 13C to 18O, provides a robust tool for determining the body temperatures of dinosaurs, but has yet to be applied across a broad phylogenetic range while accounting for the influence of paleoenvironmental conditions. Applying this method to well-preserved fossil eggshells, we find that the three major clades of dinosaurs, Ornithischia, Sauropodomorpha, and Theropoda, were characterized by warm body temperatures. Dwarf titanosaurs may have exhibited similar body temperatures to larger sauropods, although these conclusions are provisional in light of uncertainties in the taxonomic assignment of dwarf titanosaur eggshell. Regardless, our results reveal that metabolically controlled thermoregulation was the ancestral condition for Dinosauria

Eggshell geochemistry reveals ancestral metabolic thermoregulation in Dinosauria.

Studying the origin of avian thermoregulation is complicated by a lack of reliable methods for measuring body temperatures in extinct dinosaurs. Evidence from bone histology and stableisotopes often relies on uncertain assumptions about the relationship between growth rate and body temperature, or the isotopic composition (δ18O) of body water. Clumped isotope (Δ47) paleothermometry, based on binding of 13C to 18O, provides a more robust tool, but has yet to be applied across a broad phylogenetic range of dinosaurs while accounting for paleoenvironmental conditions. Applying this method to well-preserved fossil eggshells demonstrates that the three major clades of dinosaurs, Ornithischia, Sauropodomorpha, and Theropoda, were characterized by warm body temperatures. Dwarf titanosaurs may have exhibited similar body temperatures to larger sauropods, although this conclusion isprovisional, given current uncertainties in taxonomic assignment of dwarf titanosaur eggshell. Our results nevertheless reveal that metabolically controlled thermoregulation was the ancestral condition for Dinosauria

Eggshell geochemistry reveals ancestral metabolic thermoregulation in Dinosauria

Studying the origin of avian thermoregulation is complicated by a lack of reliable methods for measuring body temperatures in extinct dinosaurs. Evidence from bone histology and stableisotopes often relies on uncertain assumptions about the relationship between growth rate and body temperature, or the isotopic composition (δ18O) of body water. Clumped isotope (Δ47) paleothermometry, based on binding of 13C to 18O, provides a more robust tool, but has yet to be applied across a broad phylogenetic range of dinosaurs while accounting for paleoenvironmental conditions. Applying this method to well-preserved fossil eggshells demonstrates that the three major clades of dinosaurs, Ornithischia, Sauropodomorpha, and Theropoda, were characterized by warm body temperatures. Dwarf titanosaurs may have exhibited similar body temperatures to larger sauropods, although this conclusion isprovisional, given current uncertainties in taxonomic assignment of dwarf titanosaur eggshell. Our results nevertheless reveal that metabolically controlled thermoregulation was the ancestral condition for Dinosauria

Mandibular force profiles and tooth morphology in growth series of Albertosaurus sarcophagus and Gorgosaurus libratus (Tyrannosauridae: Albertosaurinae) provide evidence for an ontogenetic dietary shift in tyrannosaurids

The albertosaurines Albertosaurus sarcophagus and Gorgosaurus libratus are among the best represented tyrannosaurids, known from nearly complete growth series. These specimens provide an opportunity to study mandibular biomechanical properties and tooth morphology to infer changes in feeding behaviour and bite force through ontogeny in tyrannosaurids. Mandibular force profiles reveal that the symphyseal region of albertosaurines is consistently stronger in bending than the mid-dentary region, indicating that the anterior extremity of the jaws played an important role in prey capture and handling through ontogeny. The symphyseal region was better adapted to withstand torsional stresses than in most non-avian theropods, but not to the extent seen in Tyrannosaurus rex, suggesting that albertosaurine feeding behaviour may have involved less bone crushing or perhaps relatively smaller prey than in Tyrannosaurus rex. The constancy of these biomechanical properties at all known growth stages indicates that although albertosaurines maintained a similar feeding strategy through ontogeny, prey size/type had to change between juvenile and mature individuals. This ontogenetic dietary shift likely happened when individuals reached a mandibular length of ∼58 cm, a size at which teeth shift from ziphodont to incrassate in shape and bite force begins to increase exponentially. The fact that large albertosaurines were capable of generating bite forces equivalent to similar-sized tyrannosaurines suggests that no significant differences in jaw-closing musculature existed between the two clades and that the powerful bite of Tyrannosaurus rex is the result of its large body size rather than of unique adaptations related to a specialized ecology.Natural Sciences and Engineering Research Council (NSERC

Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model

Combining currently available antibiotics to optimize their use is a promising strategy to reduce treatment failures against biofilm-associated infections. Nevertheless, most assays of such combinations have been performed in vitro on planktonic bacteria exposed to constant concentrations of antibiotics over only 24 h and the synergistic effects obtained under these conditions do not necessarily predict the behavior of chronic clinical infections associated with biofilms. To improve the predictivity of in vitro combination assays for bacterial biofilms, we first adapted a previously described Hollow-fiber (HF) infection model by allowing a Staphylococcus aureus biofilm to form before drug exposure. We then mimicked different concentration profiles of amikacin and vancomycin, similar to the free plasma concentration profiles that would be observed in patients treated daily over 5 days. We assessed the ability of the two drugs, alone or in combination, to reduce planktonic and biofilm-embedded bacterial populations, and to prevent the selection of resistance within these populations. Although neither amikacin nor vancomycin exhibited any bactericidal activity on S. aureus in monotherapy, the combination had a synergistic effect and significantly reduced the planktonic bacterial population by -3.0 to -6.0 log10 CFU/mL. In parallel, no obvious advantage of the combination, as compared to amikacin alone, was demonstrated on biofilm-embedded bacteria for which the addition of vancomycin to amikacin only conferred a further maximum reduction of 0.3 log10 CFU/mL. No resistance to vancomycin was ever found whereas a few bacteria less-susceptible to amikacin were systematically detected before treatment. These resistant bacteria, which were rapidly amplified by exposure to amikacin alone, could be maintained at a low level in the biofilm population and even suppressed in the planktonic population by adding vancomycin. In conclusion, by adapting the HF model, we were able to demonstrate the different bactericidal activities of the vancomycin and amikacin combination on planktonic and biofilm-embedded bacterial populations, suggesting that, for biofilm-associated infections, the efficacy of this combination would not be much greater than with amikacin monotherapy. However, adding vancomycin could reduce possible resistance to amikacin and provide a relevant strategy to prevent the selection of antibiotic-resistant bacteria during treatments

Dinosaur eggshells from the Santonian Milk River Formation of Alberta, Canada

The North American fossil record of dinosaur eggshells for the Cretaceous is primarily restricted to formations of the middle (Albian–Cenomanian) and uppermost (Campanian–Maastrichtian) stages, with a large gap in the record for intermediate stages. Here we describe a dinosaur eggshell assemblage from a formation that represents an intermediate and poorly fossiliferous stage of the Upper Cretaceous, the Santonian Milk River Formation of southern Alberta, Canada. The Milk River eggshell assemblage contains five eggshell taxa: Continuoolithus, Porituberoolithus, Prismatoolithus, Spheroolithus, and Triprismatoolithus. These ootaxa are most similar to those reported from younger Campanian–Maastrichtian formations of the northern Western Interior than they are to ootaxa reported from older middle Cretaceous formations (i.e., predominantly Macroelongatoolithus). Characteristics of the Milk River ootaxa indicate that they are ascribable to at least one ornithopod and four small theropod species. The taxonomic affinity of the eggshell assemblage is consistent with the dinosaur fauna known based on isolated teeth and fragmentary skeletal remains from the formation, although most ornithischians and large theropods are not represented by eggshell. Relative to the Milk River Formation eggshell, similar oospecies occurring in younger Cretaceous deposits tend to be somewhat thicker, which may reflect an increase in body size of various dinosaur lineages during the Late Cretaceous.Natural Sciences and Engineering Research Council (NSERC

Use of Monte Carlo Simulations to Determine Optimal Carbapenem Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy

Pharmacokinetic/pharmacodynamic analyses with Monte Carlo simulations (MCSs) can be used to integrate prior information on model parameters into a new renal replacement therapy (RRT) to develop optimal drug dosing when pharmacokinetic trials are not feasible. This study used MCSs to determine initial doripenem, imipenem, meropenem, and ertapenem dosing regimens for critically ill patients receiving prolonged intermittent RRT (PIRRT). Published body weights and pharmacokinetic parameter estimates (nonrenal clearance, free fraction, volume of distribution, extraction coefficients) with variability were used to develop a pharmacokinetic model. MCS of 5000 patients evaluated multiple regimens in 4 different PIRRT effluent/duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis or hemofiltration) occurring at the beginning or 14–16 hours after drug infusion. The probability of target attainment (PTA) was calculated using ≥40% free serum concentrations above 4 times the minimum inhibitory concentration (MIC) for the first 48 hours. Optimal doses were defined as the smallest daily dose achieving ≥90% PTA in all PIRRT combinations. At the MIC of 2 mg/L for Pseudomonas aeruginosa, optimal doses were doripenem 750 mg every 8 hours, imipenem 1 g every 8 hours or 750 mg every 6 hours, and meropenem 1 g every 12 hours or 1 g pre‐ and post‐PIRRT. Ertapenem 500 mg followed by 500 mg post‐PIRRT was optimal at the MIC of 1 mg/L for Streptococcus pneumoniae. Incorporating data from critically ill patients receiving RRT into MCS resulted in markedly different carbapenem dosing regimens in PIRRT from those recommended for conventional RRTs because of the unique drug clearance characteristics of PIRRT. These results warrant clinical validation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134122/1/jcph727.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134122/2/jcph727_am.pd

Global Emergence of Trimethoprim/Sulfamethoxazole Resistance in Stenotrophomonas maltophilia Mediated by Acquisition of sul Genes

The first sul2 genes have been found in S. maltophilia from several different countries

Cancellous bone and theropod dinosaur locomotion. Part III—Inferring posture and locomotor biomechanics in extinct theropods, and its evolution on the line to birds

This paper is the last of a three-part series that investigates the architecture of cancellous bone in the main hindlimb bones of theropod dinosaurs, and uses cancellous bone architectural patterns to infer locomotor biomechanics in extinct non-avian species. Cancellous bone is highly sensitive to its prevailing mechanical environment, and may therefore help further understanding of locomotor biomechanics in extinct tetrapod vertebrates such as dinosaurs. Here in Part III, the biomechanical modelling approach derived previously was applied to two species of extinct, non-avian theropods, Daspletosaurus torosus and Troodon formosus. Observed cancellous bone architectural patterns were linked with quasi-static, three-dimensional musculoskeletal and finite element models of the hindlimb of both species, and used to derive characteristic postures that best aligned continuum-level principal stresses with cancellous bone fabric. The posture identified for Daspletosaurus was largely upright, with a subvertical femoral orientation, whilst that identified for Troodon was more crouched, but not to the degree observed in extant birds. In addition to providing new insight on posture and limb articulation, this study also tested previous hypotheses of limb bone loading mechanics and muscular control strategies in non-avian theropods, and how these aspects evolved on the line to birds. The results support the hypothesis that an upright femoral posture is correlated with bending-dominant bone loading and abduction-based muscular support of the hip, whereas a crouched femoral posture is correlated with torsion-dominant bone loading and long-axis rotation-based muscular support. Moreover, the results of this study also support the inference that hindlimb posture, bone loading mechanics and muscular support strategies evolved in a gradual fashion along the line to extant birds