Evolution of arboreality and fossoriality in squirrels and aplodontid rodents: Insights from the semicircular canals of fossil rodents.

Reconstructing locomotor behaviour for fossil animals is typically done with postcranial elements. However, for species only known from cranial material, locomotor behaviour is difficult to reconstruct. The semicircular canals (SCCs) in the inner ear provide insight into an animal's locomotor agility. A relationship exists between the size of the SCCs relative to body mass and the jerkiness of an animal's locomotion. Additionally, studies have also demonstrated a relationship between SCC orthogonality and angular head velocity. Here, we employ two metrics for reconstructing locomotor agility, radius of curvature dimensions and SCC orthogonality, in a sample of twelve fossil rodents from the families Ischyromyidae, Sciuridae and Aplodontidae. The method utilizing radius of curvature dimensions provided a reconstruction of fossil rodent locomotor behaviour that is more consistent with previous studies assessing fossil rodent locomotor behaviour compared to the method based on SCC orthogonality. Previous work on ischyromyids suggests that this group displayed a variety of locomotor modes. Members of Paramyinae and Ischyromyinae have relatively smaller SCCs and are reconstructed to be relatively slower compared to members of Reithroparamyinae. Early members of the Sciuroidea clade including the sciurid Cedromus wilsoni and the aplodontid Prosciurus relictus are reconstructed to be more agile than ischyromyids, in the range of extant arboreal squirrels. This reconstruction supports previous inferences that arboreality was likely an ancestral trait for this group. Derived members of Sciuridae and Aplodontidae vary in agility scores. The fossil squirrel Protosciurus cf. rachelae is inferred from postcranial material as arboreal, which is in agreement with its high agility, in the range of extant arboreal squirrels. In contrast, the fossil aplodontid Mesogaulus paniensis has a relatively low agility score, similar to the fossorial Aplodontia rufa, the only living aplodontid rodent. This result is in agreement with its postcranial reconstruction as fossorial and with previous indications that early aplodontids were more arboreal than their burrowing descendants.

Salmeterol/fluticasone through breath-actuated inhaler versus pMDI: a randomized, double-blind, 12 weeks study.

OBJECTIVE: Salmeterol/fluticasone combination (SFC) formulated in a breath-actuated inhaler (BAI) overcomes the co-ordination problem associated with the pressurized-metered dose inhaler (pMDIs). Our aim was to compare the efficacy and the safety of SFC given through the BAI versus the conventional pMDI in moderate-to-severe asthmatics. METHODS: In this randomized, double-blind, double-dummy, prospective, active-controlled, parallel group, multicenter, 12 weeks study, 150 asthmatics were randomized to receive SFC (25/125 mcg) through either BAI or pMDI. The primary efficacy endpoint was mean change in pre-dose morning PEFR value at 12 weeks and the secondary efficacy endpoints included, mean change in FEV(1), pre-bronchodilator FVC, pre-dose morning and evening PEFR, symptom scores at 2, 4, 8, and 12 weeks. Patient preferences for device and safety were also assessed. RESULTS: At 12 weeks, the mean change in pre-dose morning PEFR in BAI and pMDI groups was 50.72 L/min and 48.82 L/min, respectively (p < 0.0001; both groups) and the difference between the two groups was not significant. Both the treatment groups showed a statistically significant improvement in secondary endpoints at all-time points compared with baseline. The usability questionnaire assessment results showed that the BAI device was preferred by 75% of patients as compared with 25% preferring pMDI. SFC in both BAI and pMDI devices was found to be safe and well tolerated. CONCLUSION: This is the first study to demonstrate that SFC given through the BAI produces comparable efficacy and safety endpoints as pMDI. Additionally, BAI was the preferred inhaler by patients compared to conventional pMDI.

Locomotor behavior and hearing sensitivity in an early lagomorph reconstructed from the bony labyrinth.

The structure of the bony labyrinth is highly informative with respect to locomotor agility (semicircular canals [SCC]) and hearing sensitivity (cochlear and oval windows). Here, we reconstructed the agility and hearing sensitivity of the stem lagomorph Megalagus turgidus from the early Oligocene of the Brule Formation of Nebraska (USA). Megalagus has proportionally smaller SCCs with respect to its body mass compared with most extant leporids but within the modern range of variability, suggesting that it was less agile than most of its modern relatives. A level of agility for Megalagus within the range of modern rabbits is consistent with the evidence from postcranial elements. The hearing sensitivity for Megalagus is in the range of extant lagomorphs for both low- and high-frequency sounds. Our data show that by the early Oligocene stem lagomorphs had already attained fundamentally rabbit-like hearing sensitivity and locomotor behavior, even though Megalagus was not a particularly agile lagomorph. This is likely because Megalagus was more of a woodland dweller than an open-habitat runner. The study of sensory evolution in Lagomorpha is practically unknown, and these results provide first advances in understanding the primitive stages for the order and how the earliest members of this clade perceived their environment.